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N6-methyladenosine-modified circSLCO1B3 promotes intrahepatic cholangiocarcinoma progression via regulating HOXC8 and PD-L1 J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-20 Jing Li, Xiaohong Xu, Kaihao Xu, Xueliang Zhou, Kunpeng Wu, Yuan Yao, Zaoqu Liu, Chen Chen, Ling Wang, Zhenqiang Sun, Dechao Jiao, Xinwei Han
Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality and poor prognosis. Important function invests circRNAs with tremendous potential in biomarkers and therapeutic targets. Nevertheless, it is still unknown how circRNAs contribute to the evolution of ICC. CircRNAs in paired ICC and adjacent tissues
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Unveiling the gastric microbiota: implications for gastric carcinogenesis, immune responses, and clinical prospects J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-19 Zhiyi Liu, Dachuan Zhang, Siyu Chen
High-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes
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The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-19 Wenbo Ma, Jinqiang Zhang, Weina Chen, Nianli Liu, Tong Wu
Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with poor prognosis. Further mechanistic insights into the molecular mechanisms of CCA are needed to develop more effective target therapy. The expression of the histone lysine acetyltransferase KAT2B in human CCA was analyzed in human CCA tissues. CCA xenograft was developed by inoculation of human CCA cells with or without
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PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt–β-catenin pathway J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-18 Peng Yu, Tutu Xu, Wenmeng Ma, Xiang Fang, Yue Bao, Chengran Xu, Jinhai Huang, Yongqing Sun, Guangyu Li
Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy
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CCAAT enhancer binding protein delta activates vesicle associated membrane protein 3 transcription to enhance chemoresistance and extracellular PD-L1 expression in triple-negative breast cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-16 Yan Zhao, Yangyang Yu, Xiangmin Li, Ayao Guo
Chemoresistance and immunosuppression are two major obstacles in the current anti-cancer treatments. This study investigates the involvements of a CCAAT enhancer binding protein delta (CEBPD)/vesicle associated membrane protein 3 (VAMP3) axis in paclitaxel (PTX) resistance and immune evasion in triple-negative breast cancer (TNBC). PTX resistance-related genes were screened by bioinformatics. CEBPD
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Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-16 Wenxin Zhang, Lu Chen, Jiafeng Liu, Bicui Chen, Huanying Shi, Haifei Chen, Huijie Qi, Zimei Wu, Xiang Mao, Xinhai Wang, Yuxin Huang, Jiyifan Li, Zheng Yu, Mingkang Zhong, Tianxiao Wang, Qunyi Li
The efficacy of anti-PD-1 therapy is primarily hindered by the limited T-cell immune response rate and immune evasion capacity of tumor cells. Autophagy-related protein 7 (ATG7) plays an important role in autophagy and it has been linked to cancer. However, the role of ATG7 in the effect of immune checkpoint blockade (ICB) treatment on high microsatellite instability (MSI-H)/mismatch repair deficiency
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Correction: Targeting of focal adhesion kinase enhances the immunogenic cell death of PEGylated liposome doxorubicin to optimize therapeutic responses of immune checkpoint blockade J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-16 Baoyuan Zhang, Ning Li, Jiaming Gao, Yuxi Zhao, Jun Jiang, Shuang Xie, Cuiping Zhang, Qingyu Zhang, Leo Liu, Zaiqi Wang, Dongmei Ji, Lingying Wu, Ruibao Ren
Correction: J Exp Clin Cancer Res 43, 51 (2024) https://doi.org/10.1186/s13046-024-02974-4 Following publication of the original article [1], Baoyuan Zhang, Ning Li, Jiaming Gao were not captured as co-first authors and equal contributors. This was not declared in the accepted manuscript and the authors failed to correct this during proofing. The correction does not affect the overall result or conclusion
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Augmented ERO1α upon mTORC1 activation induces ferroptosis resistance and tumor progression via upregulation of SLC7A11 J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-13 Zixi Wang, Huaiyuan Zong, Weiwei Liu, Wei Lin, Anjiang Sun, Zhao Ding, Xu Chen, Xiaofeng Wan, Yanyan Liu, Zhongdong Hu, Hongbing Zhang, Hongwu Li, Yehai Liu, Dapeng Li, Sumei Zhang, Xiaojun Zha
The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical
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METTL3 recruiting M2-type immunosuppressed macrophages by targeting m6A-SNAIL-CXCL2 axis to promote colorectal cancer pulmonary metastasis J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-11 Peng Ouyang, Kang Li, Wei Xu, Caiyun Chen, Yangdong Shi, Yao Tian, Jin Gong, Zhen Bao
The regulatory role of N6-methyladenosine (m6A) modification in the onset and progression of cancer has garnered increasing attention in recent years. However, the specific role of m6A modification in pulmonary metastasis of colorectal cancer remains unclear. This study identified differential m6A gene expression between primary colorectal cancer and its pulmonary metastases using transcriptome sequencing
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HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-11 Svenja Schneegans, Jana Löptien, Angelika Mojzisch, Desirée Loreth, Oliver Kretz, Christoph Raschdorf, Annkathrin Hanssen, Antonia Gocke, Bente Siebels, Karthikeyan Gunasekaran, Yi Ding, Leticia Oliveira-Ferrer, Laura Brylka, Thorsten Schinke, Hartmut Schlüter, Ilkka Paatero, Hannah Voß, Stefan Werner, Klaus Pantel, Harriet Wikman
Metastasis is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC) patients. We previously showed that low HERC5 expression predicts early tumor dissemination and a dismal prognosis in NSCLC patients. Here, we performed functional studies to unravel the mechanism underlying the “metastasis-suppressor” effect of HERC5, with a focus on mitochondrial metabolism pathways. We
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A paclitaxel-hyaluronan conjugate (ONCOFID-P-B™) in patients with BCG-unresponsive carcinoma in situ of the bladder: a dynamic assessment of the tumor microenvironment J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-10 Anna Tosi, Beatrice Parisatto, Enrico Gaffo, Stefania Bortoluzzi, Antonio Rosato
The intravesical instillation of the paclitaxel-hyaluronan conjugate ONCOFID-P-B™ in patients with bacillus Calmette-Guérin (BCG)-unresponsive bladder carcinoma in situ (CIS; NCT04798703 phase I study), induced 75 and 40% of complete response (CR) after 12 weeks of intensive phase and 12 months of maintenance phase, respectively. The aim of this study was to provide a detailed description of the tumor
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Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-10 Yaya Qiao, Meng Su, Huifang Zhao, Huanle Liu, Chenxi Wang, Xintong Dai, Lingling Liu, Guangju Liu, Huanran Sun, Mingming Sun, Jiyan Wang, Zhen Li, Jun Fan, Quan Zhang, Chunshen Li, Fangmin Situ, Jun Xue, Zhenghu Jia, Chunze Zhang, Shuai Zhang, Changliang Shan
Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive.
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A phenotypic screening approach to target p60AmotL2-expressing invasive cancer cells J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-09 Pedro Fonseca, Weiyingqi Cui, Nona Struyf, Le Tong, Ayushi Chaurasiya, Felipe Casagrande, Honglei Zhao, Dinura Fernando, Xinsong Chen, Nicholas P. Tobin, Brinton Seashore-Ludlow, Andreas Lundqvist, Johan Hartman, Anita Göndör, Päivi Östling, Lars Holmgren
Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive
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HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-08 Daqin Suo, Xiaoling Gao, Qingyun Chen, Tingting Zeng, Jiarong Zhan, Guanghui Li, Yinli Zheng, Senlin Zhu, Jingping Yun, Xin-Yuan Guan, Yan Li
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune
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GPR65 sensing tumor-derived lactate induces HMGB1 release from TAM via the cAMP/PKA/CREB pathway to promote glioma progression J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-04 Chaolong Yan, Zijiang Yang, Pin Chen, Yuyang Yeh, Chongjing Sun, Tao Xie, Wei Huang, Xiaobiao Zhang
Lactate has emerged as a critical regulator within the tumor microenvironment, including glioma. However, the precise mechanisms underlying how lactate influences the communication between tumor cells and tumor-associated macrophages (TAMs), the most abundant immune cells in glioma, remain poorly understood. This study aims to elucidate the impact of tumor-derived lactate on TAMs and investigate the
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RBM10 C761Y mutation induced oncogenic ASPM isoforms and regulated β-catenin signaling in cholangiocarcinoma J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-04 Jiang Chang, Yaodong Zhang, Tao Zhou, Qian Qiao, Jijun Shan, Yananlan Chen, Wangjie Jiang, Yirui Wang, Shuochen Liu, Yuming Wang, Yue Yu, Changxian Li, Xiangcheng Li
Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary tract cancer. Our previous CCA mutation pattern study focused on genes in the post-transcription modification process, among which the alternative splicing factor RBM10 captured our attention. However, the roles of RBM10 wild type and mutations in CCA remain unclear. RBM10 mutation spectrum in CCA was clarified using our initial data
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Mesothelin promotes brain metastasis of non-small cell lung cancer by activating MET J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-03 Shengkai Xia, Wenzhe Duan, Mingxin Xu, Mengqi Li, Mengyi Tang, Song Wei, Manqing Lin, Encheng Li, Wenwen Liu, Qi Wang
Brain metastasis (BM) is common among cases of advanced non-small cell lung cancer (NSCLC) and is the leading cause of death for these patients. Mesothelin (MSLN), a tumor-associated antigen expressed in many solid tumors, has been reported to be involved in the progression of multiple tumors. However, its potential involvement in BM of NSCLC and the underlying mechanism remain unknown. The expression
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Oncolytic adenovirus encoding apolipoprotein A1 suppresses metastasis of triple-negative breast cancer in mice J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-03 Jie Dong, Lingkai Kong, Shiqun Wang, Mao Xia, Yenan Zhang, Jingyi Wu, Fuming Yang, Shuguang Zuo, Jiwu Wei
Dysregulation of cholesterol metabolism is associated with the metastasis of triple-negative breast cancer (TNBC). Apolipoprotein A1 (ApoA1) is widely recognized for its pivotal role in regulating cholesterol efflux and maintaining cellular cholesterol homeostasis. However, further exploration is needed to determine whether it inhibits TNBC metastasis by affecting cholesterol metabolism. Additionally
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Investigating the impact of regulatory B cells and regulatory B cell-related genes on bladder cancer progression and immunotherapeutic sensitivity J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-02 Jiawei Zhou, Ranran Zhou, Yuanchao Zhu, Shikai Deng, Bahaerguli Muhuitijiang, Chengyao Li, Xiaojun Shi, Ling Zhang, Wanlong Tan
Regulatory B cells (Bregs), a specialized subset of B cells that modulate immune responses and maintain immune tolerance in malignant tumors, have not been extensively investigated in the context of bladder cancer (BLCA). This study aims to elucidate the roles of Bregs and Breg-related genes in BLCA. We assessed Breg infiltration levels in 34 pairs of BLCA and corresponding paracancerous tissues using
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A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301) J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-02 Pavlina Spiliopoulou, Farasat Kazmi, Francesca Aroldi, Thomas Holmes, David Thompson, Lucinda Griffiths, Cathy Qi, Matthew Parkes, Simon Lord, Gareth J. Veal, David J. Harrison, Vicky M. Coyle, Jill Graham, Thomas R. Jeffry Evans, Sarah P. Blagden
5-fluorouracil (5-FU) is inefficiently converted to the active anti-cancer metabolite, fluorodeoxyuridine-monophosphate (FUDR-MP), is associated with dose-limiting toxicities and challenging administration schedules. NUC-3373 is a phosphoramidate nucleotide analog of fluorodeoxyuridine (FUDR) designed to overcome these limitations and replace fluoropyrimidines such as 5-FU. NUC-3373 was administered
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Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-02 Zhengyue Zhang, Yanjie Zhang
Cancer stem cells (CSCs) were first discovered in the 1990s, revealing the mysteries of cancer origin, migration, recurrence and drug-resistance from a new perspective. The expression of pluripotent genes and complex signal regulatory networks are significant features of CSC, also act as core factors to affect the characteristics of CSC. Transcription is a necessary link to regulate the phenotype and
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Tumor suppressor role of the complement inhibitor CSMD1 and its role in TNF-induced neuroinflammation in gliomas J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-01 Emre Can Tuysuz, Eleni Mourati, Rebecca Rosberg, Aleksandra Moskal, Chrysostomi Gialeli, Elinn Johansson, Valeria Governa, Mattias Belting, Alexander Pietras, Anna M. Blom
The complement inhibitor CSMD1 acts as a tumor suppressor in various types of solid cancers. Despite its high level of expression in the brain, its function in gliomas, malignant brain tumors originating from glial cells, has not been investigated. Three cohorts of glioma patients comprising 1500 patients were analyzed in our study along with their clinical data. H4, U-118 and U-87 cell lines were
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A high-content screen of FDA approved drugs to enhance CAR T cell function: ingenol-3-angelate improves B7-H3-CAR T cell activity by upregulating B7-H3 on the target cell surface via PKCα activation J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-01 Ha Won Lee, Carla O’Reilly, Alex N. Beckett, Duane G. Currier, Taosheng Chen, Christopher DeRenzo
CAR T cell therapy is a promising approach to improve outcomes and decrease toxicities for patients with cancer. While extraordinary success has been achieved using CAR T cells to treat patients with CD19-positive malignancies, multiple obstacles have so far limited the benefit of CAR T cell therapy for patients with solid tumors. Novel manufacturing and engineering approaches show great promise to
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Liquid biopsy techniques and lung cancer: diagnosis, monitoring and evaluation J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-01 Fei Ren, Qian Fei, Kun Qiu, Yuanjie Zhang, Heyang Zhang, Lei Sun
Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment
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Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-04-01 Xing Li, Shiyu Sun, Wansong Zhang, Ziwei Liang, Yitong Fang, Tianhu Sun, Yong Wan, Xingcong Ma, Shuqun Zhang, Yang Xu, Ruilin Tian
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related
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Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-27 Zengxu Wang, Keith L. Kirkwood, Yao Wang, Weidong Du, Shanfeng Lin, Wanhang Zhou, Cong Yan, Jiaxing Gao, Zhenning Li, Changfu Sun, Fayu Liu
Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics
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Correction: A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-26 Bolin Wang, Jinli Pei, Shengnan Xu, Jie Liu, Jinming Yu
Correction: J Exp Clin Cancer Res (2024) 43:74 https://doi.org/10.1186/s13046-024-02994-0 Following publication of the original article [1], errors were spotted particularly in Funding section. The correct funding statement is stated below: Incorrect Funding This work was supported by the National Natural Science Foundation of China (Grant Nos. 81,627,901, 82,203,014, 81,972,863, (Grant Nos. 81,627
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Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-26 Simona Camorani, Alessandra Caliendo, Elena Morrone, Lisa Agnello, Matteo Martini, Monica Cantile, Margherita Cerrone, Antonella Zannetti, Massimo La Deda, Monica Fedele, Loredana Ricciardi, Laura Cerchia
Based on the established role of cancer-stroma cross-talk in tumor growth, progression and chemoresistance, targeting interactions between tumor cells and their stroma provides new therapeutic approaches. Dual-targeted nanotherapeutics selectively acting on both tumor and stromal cells may overcome the limits of tumor cell-targeting single-ligand nanomedicine due to the complexity of the tumor microenvironment
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PELI1: key players in the oncogenic characteristics of pancreatic Cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-25 Xiaobin Fei, Changhao Zhu, Peng Liu, Songbai Liu, Likun Ren, Rishang Lu, Junyi Hou, Yongjia Gao, Xing Wang, Yaozhen Pan
Pancreatic cancer (PC) is a highly malignant gastrointestinal tumor, which is characterized by difficulties in early diagnosis, early metastasis, limited therapeutic response and a grim prognosis. Therefore, it is imperative to explore potential therapeutic targets for PC. Currently, although the involvement of the Pellino E3 Ubiquitin Protein Ligase 1 (PELI1) in the human growth of some malignant
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Ropivacaine as a novel AKT1 specific inhibitor regulates the stemness of breast cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-25 Lin Ding, Hui Jiang, Qiangwei Li, Qiushuang Li, Tian-Tian Zhang, Limeng Shang, Bin Xie, Yaling Zhu, Keshuo Ding, Xuanming Shi, Tao Zhu, Yong Zhu
Ropivacaine, a local anesthetic, exhibits anti-tumor effects in various cancer types. However, its specific functions and the molecular mechanisms involved in breast cancer cell stemness remain elusive. The effects of ropivacaine on breast cancer stemness were investigated by in vitro and in vivo assays (i.e., FACs, MTT assay, mammosphere formation assay, transwell assays, western blot, and xenograft
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CDKL1 potentiates the antitumor efficacy of radioimmunotherapy by binding to transcription factor YBX1 and blocking PD-L1 expression in lung cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-22 Zixuan Li, Huichan Xue, Jinsong Li, Zhikun Zheng, Zhiwei Liu, Xiaorong Dong, Hongbo Wang, Jing Chen, Shuangbing Xu
The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation
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Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-22 Christophe Deben, Laurie Freire Boullosa, Felicia Rodrigues Fortes, Edgar Cardenas De La Hoz, Maxim Le Compte, Sofie Seghers, Marc Peeters, Steve Vanlanduit, Abraham Lin, Krijn K. Dijkstra, Paul Van Schil, Jeroen M. H. Hendriks, Hans Prenen, Geert Roeyen, Filip Lardon, Evelien Smits
This study explores the repurposing of Auranofin (AF), an anti-rheumatic drug, for treating non-small cell lung cancer (NSCLC) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). Drug repurposing in oncology offers a cost-effective and time-efficient approach to developing new cancer therapies. Our research focuses on evaluating AF's selective cytotoxicity against cancer cells, identifying
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Cross-reactive CD8+ T cell responses to tumor-associated antigens (TAAs) and homologous microbiota-derived antigens (MoAs) J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-20 Beatrice Cavalluzzo, Marie Christine Viuff, Siri Amanda Tvingsholm, Concetta Ragone, Carmen Manolio, Angela Mauriello, Franco M. Buonaguro, Maria Lina Tornesello, Francesco Izzo, Alessandro Morabito, Sine Reker Hadrup, Maria Tagliamonte, Luigi Buonaguro
We have recently shown extensive sequence and conformational homology between tumor-associated antigens (TAAs) and antigens derived from microorganisms (MoAs). The present study aimed to assess the breadth of T-cell recognition specific to MoAs and the corresponding TAAs in healthy subjects (HS) and patients with cancer (CP). A library of > 100 peptide-MHC (pMHC) combinations was used to generate DNA-barcode
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Unveiling CXCR2 as a promising therapeutic target in renal cell carcinoma: exploring the immunotherapeutic paradigm shift through its inhibition by RCT001 J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-19 Christopher Montemagno, Arnaud Jacquel, Charlotte Pandiani, Olivia Rastoin, Rosie Dawaliby, Thomas Schmitt, Maxence Bourgoin, Héliciane Palenzuela, Anne-Laure Rossi, Damien Ambrosetti, Jerome Durivault, Frederic Luciano, Delphine Borchiellini, Julie Le Du, Leticia Christina Pires Gonçalves, Patrick Auberger, Rachid Benhida, Lisa Kinget, Benoit Beuselinck, Cyril Ronco, Gilles Pagès, Maeva Dufies
In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies. We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy
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Anaplastic thyroid cancer spheroids as preclinical models to test therapeutics J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-19 Jiangnan Hu, Kaili Liu, Chandrayee Ghosh, Tejinder Pal Khaket, Helen Shih, Electron Kebebew
Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer. Despite advances in tissue culture techniques, a robust model for ATC spheroid culture is yet to be developed. In this study, we created an efficient and cost-effective 3D tumor spheroids culture system from human ATC cells and existing cell lines that better mimic patient tumors and that can enhance our understanding of in vivo
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The localization, origin, and impact of platelets in the tumor microenvironment are tumor type-dependent J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-16 Ophélie Le Chapelain, Soumaya Jadoui, Angèle Gros, Samir Barbaria, Keltouma Benmeziane, Véronique Ollivier, Sébastien Dupont, Mialitiana Solo Nomenjanahary, Sabrina Mavouna, Jasmina Rogozarski, Marie-Anne Mawhin, Giuseppina Caligiuri, Sandrine Delbosc, Françoise Porteu, Bernhard Nieswandt, Pierre H Mangin, Yacine Boulaftali, Benoit Ho-Tin-Noé
How platelets interact with and influence the tumor microenvironment (TME) remains poorly characterized. We compared the presence and participation of platelets in the TME of two tumors characterized by highly different TME, PyMT AT-3 mammary tumors and B16F1 melanoma. We show that whereas firmly adherent platelets continuously line tumor vessels of both AT-3 and B16F1 tumors, abundant extravascular
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Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-16 Xueping Lei, Zhan Li, Manting Huang, Lijuan Huang, Yong Huang, Sha Lv, Weisong Zhang, Zhuowen Chen, Yuanyu Ke, Songpei Li, Jingfei Chen, Xiangyu Yang, Qiudi Deng, Junshan Liu, Xiyong Yu
Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene
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Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-16 Yo-Ting Tsai, Jeffrey Schlom, Renee N. Donahue
The paradigm of non-small cell lung cancer (NSCLC) treatment has been profoundly influenced by the development of immune checkpoint inhibitors (ICI), but the range of clinical responses observed among patients poses significant challenges. To date, analyses of tumor biopsies are the only parameter used to guide prognosis to ICI therapy. Tumor biopsies, however, are often difficult to obtain and tissue-based
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Validation of a multiomic model of plasma extracellular vesicle PD-L1 and radiomics for prediction of response to immunotherapy in NSCLC J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-15 Diego de Miguel‑Perez, Murat Ak, Priyadarshini Mamindla, Alessandro Russo, Serafettin Zenkin, Nursima Ak, Vishal Peddagangireddy, Luis Lara‑Mejia, Muthukumar Gunasekaran, Andres F. Cardona, Aung Naing, Fred R. Hirsch, Oscar Arrieta, Rivka R. Colen, Christian Rolfo
Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response
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Correction: RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-14 Yu-Jiao Zhou, Min-Li Yang, Xin He, Hui-Ying Gu, Ji-Hua Ren, Sheng-Tao Cheng, Zhou Fu, Zhen-Zhen Zhang, Juan Chen
Correction: J Exp Clin Cancer Res 43, 45 (2024) https://doi.org/10.1186/s13046-023-02929-1 Following publication of the original article [1], errors were spotted particularly in Fig. 6, specifically: Fig. 6b – upper panels, incorrect representative image used for migration transwell assays of Huh7 cells transfected with EV Fig. 6d – lower panels, incorrect representative image used for invasion transwell
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C/EBPα-p30 confers AML cell susceptibility to the terminal unfolded protein response and resistance to Venetoclax by activating DDIT3 transcription J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-13 Mengbao Du, Mowang Wang, Meng Liu, Shan Fu, Yu Lin, Yankun Huo, Jian Yu, Xiaohong Yu, Chong Wang, Haowen Xiao, Limengmeng Wang
Acute myeloid leukemia (AML) with biallelic (CEBPAbi) as well as single mutations located in the bZIP region is associated with a favorable prognosis, but the underlying mechanisms are still unclear. Here, we propose that two isoforms of C/EBPα regulate DNA damage-inducible transcript 3 (DDIT3) transcription in AML cells corporately, leading to altered susceptibility to endoplasmic reticulum (ER) stress
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Functionally-instructed modifiers of response to ATR inhibition in experimental glioma J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-12 Bianca Walter, Sophie Hirsch, Laurence Kuhlburger, Aaron Stahl, Leonard Schnabel, Silas Wisser, Lara A. Haeusser, Foteini Tsiami, Sarah Plöger, Narges Aghaallaei, Advaita M Dick, Julia Skokowa, Christian Schmees, Markus Templin, Katja Schenke-Layland, Marcos Tatagiba, Sven Nahnsen, Daniel J. Merk, Ghazaleh Tabatabai
The DNA damage response (DDR) is a physiological network preventing malignant transformation, e.g. by halting cell cycle progression upon DNA damage detection and promoting DNA repair. Glioblastoma are incurable primary tumors of the nervous system and DDR dysregulation contributes to acquired treatment resistance. Therefore, DDR targeting is a promising therapeutic anti-glioma strategy. Here, we investigated
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Combined IL6 and CCR2 blockade potentiates antitumor activity of NK cells in HPV-negative head and neck cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-12 Fan Yang, Chenyang Yuan, Fanghui Chen, Zhaohui S. Qin, Nicole C. Schmitt, Gregory B. Lesinski, Nabil F. Saba, Yong Teng
While T cell-activating immunotherapies against recurrent head and neck squamous cell carcinoma (HNSCC) have shown impressive results in clinical trials, they are often ineffective in the majority of patients. NK cells are potential targets for immunotherapeutic intervention; however, the setback in monalizumab-based therapy in HNSCC highlights the need for an alternative treatment to enhance their
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Correction: The epigenetic downregulation of LncGHRLOS mediated by RNA m6A methylase ZCCHC4 promotes colorectal cancer tumorigenesis J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-12 Ke Chen, Jingcheng Zhang, Lei Meng, Lingshang Kong, Ming Lu, Zhengguang Wang, Wenbin Wang
Correction: J Exp Clin Cancer Res 43, 44 (2024) https://doi.org/10.1186/s13046-024-02965-5 Following publication of the original article [1], errors were spotted in some of the entries in Table 1, Table 2 and Fig. 6. Specifically: Table number Row Column Incorrect data Correct data 1 Positive lymph nodes—≥ 3 Low (n = 68) 15 20 1 Positive lymph nodes—≥ 3 High (n = 175) 101 84 1 Positive lymph nodes—< 3
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TRF2 as novel marker of tumor response to taxane-based therapy: from mechanistic insight to clinical implication J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-09 Sara Iachettini, Irene Terrenato, Manuela Porru, Serena Di Vito, Angela Rizzo, Carmen D’Angelo, Eleonora Petti, Roberto Dinami, Carmen Maresca, Anna Di Benedetto, Aldo Palange, Antonino Mulè, Angela Santoro, Antonella Palazzo, Paola Fuso, Antonella Stoppacciaro, Patrizia Vici, Lorena Filomeno, Francesca Sofia Di Lisa, Teresa Arcuri, Eriseld Krasniqi, Alessandra Fabi, Annamaria Biroccio, Pasquale Zizza
Breast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) – the most aggressive BC form – is refractory to endocrine and most of the target therapies. In this view, taxane-based therapy still represents the elective strategy for the treatment of this tumor. However, due variability
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A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-08 Bolin Wang, Jinli Pei, Shengnan Xu, Jie Liu, Jinming Yu
Glutamine metabolism plays a pivotal role in cancer progression, immune cell function, and the modulation of the tumor microenvironment. Dysregulated glutamine metabolism has been implicated in cancer development and immune responses, supported by mounting evidence. Cancer cells heavily rely on glutamine as a critical nutrient for survival and proliferation, while immune cells require glutamine for
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TGF-β-activated circRYK drives glioblastoma progression by increasing VLDLR mRNA expression and stability in a ceRNA- and RBP-dependent manner J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-08 Yuhang Wang, Binbin Wang, Wenping Cao, Xiupeng Xu
The TGF-β signalling pathway is intricately associated with the progression of glioblastoma (GBM). The objective of this study was to examine the role of circRNAs in the TGF-β signalling pathway. In our research, we used transcriptome analysis to search for circRNAs that were activated by TGF-β. After confirming the expression pattern of the selected circRYK, we carried out in vitro and in vivo cell
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S100A9+CD14+ monocytes contribute to anti-PD-1 immunotherapy resistance in advanced hepatocellular carcinoma by attenuating T cell-mediated antitumor function J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-08 Xiaoxuan Tu, Longxian Chen, Yi Zheng, Chenglin Mu, Zhiwei Zhang, Feiyu Wang, Yiqing Ren, Yingxin Duan, Hangyu Zhang, Zhou Tong, Lulu Liu, Xunqi Sun, Peng Zhao, Lie Wang, Xinhua Feng, Weijia Fang, Xia Liu
The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical
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Biological mechanisms and clinical significance of endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) in human cancer J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-08 Peng Chen, Amit Sharma, Hans Weiher, Ingo G.H. Schmidt-Wolf
A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate
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Inhibition of MER proto-oncogene tyrosine kinase by an antisense oligonucleotide enhances treatment efficacy of immunoradiotherapy J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-06 Yun Hu, Alexey Revenko, Hampartsoum Barsoumian, Genevieve Bertolet, Natalie Wall Fowlkes, Hadi Maazi, Morgan Maureen Green, Kewen He, Duygu Sezen, Tiffany A. Voss, Claudia S Kettlun Leyton, Fatemeh Masrorpour, Zahid Rafiq, Nahum Puebla-Osorio, Carola Leuschner, Robert MacLeod, Maria Angelica Cortez, James W. Welsh
The combination of radiotherapy and immunotherapy (immunoradiotherapy) has been increasingly used for treating a wide range of cancers. However, some tumors are resistant to immunoradiotherapy. We have previously shown that MER proto-oncogene tyrosine kinase (MerTK) expressed on macrophages mediates resistance to immunoradiotherapy. We therefore sought to develop therapeutics that can mitigate the
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KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-05 Hongshi Cai, Jianfeng Liang, Yaoqi Jiang, Ziyi Wang, Hongyu Li, Wenjin Wang, Cheng Wang, Jinsong Hou
Head and neck squamous carcinoma (HNSCC) is known for its high aggressiveness and susceptibility to cervical lymph node metastasis, which greatly contributes to its poor prognosis. During tumorigenesis, many types of cancer cells acquire oncogenic super-enhancers (SEs) that drive the overexpression of oncogenes, thereby maintaining malignant progression. This study aimed to identify and validate the
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MUC20 regulated by extrachromosomal circular DNA attenuates proteasome inhibitor resistance of multiple myeloma by modulating cuproptosis J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-05 Xiaobin Wang, Yingqing Shi, Hua Shi, Xiaoyu Liu, Aijun Liao, Zhuogang Liu, Robert Z. Orlowski, Rui Zhang, Huihan Wang
Proteasome inhibitors (PIs) are one of the most important classes of drugs for the treatment of multiple myeloma (MM). However, almost all patients with MM develop PI resistance, resulting in therapeutic failure. Therefore, the mechanisms underlying PI resistance in MM require further investigation. We used several MM cell lines to establish PI-resistant MM cell lines. We performed RNA microarray and
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Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-01 Bisheng Cheng, Lingfeng Li, Tianlong Luo, Qiong Wang, Yong Luo, Shoumin Bai, Kaiwen Li, Yiming Lai, Hai Huang
Docetaxel resistance represents a significant obstacle in the treatment of prostate cancer. The intricate interplay between cytokine signalling pathways and transcriptional control mechanisms in cancer cells contributes to chemotherapeutic resistance, yet the underlying molecular determinants remain only partially understood. This study elucidated a novel resistance mechanism mediated by the autocrine
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GMP-manufactured CRISPR/Cas9 technology as an advantageous tool to support cancer immunotherapy J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-01 M Caforio, S Iacovelli, C Quintarelli, F Locatelli, Valentina Folgiero
CRISPR/Cas9 system to treat human-related diseases has achieved significant results and, even if its potential application in cancer research is improving, the application of this approach in clinical practice is still a nascent technology. CRISPR/Cas9 technology is not yet used as a single therapy to treat tumors but it can be combined with traditional treatment strategies to provide personalized
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Tight junction protein cingulin variant is associated with cancer susceptibility by overexpressed IQGAP1 and Rac1-dependent epithelial-mesenchymal transition J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-01 Yi-Ting Huang, Ya-Ting Hsu, Pei-Ying Wu, Yu-Min Yeh, Peng-Chan Lin, Keng-Fu Hsu, Meng-Ru Shen
Cingulin (CGN) is a pivotal cytoskeletal adaptor protein located at tight junctions. This study investigates the link between CGN mutation and increased cancer susceptibility through genetic and mechanistic analyses and proposes a potential targeted therapeutic approach. In a high-cancer-density family without known pathogenic variants, we performed tumor-targeted and germline whole-genome sequencing
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JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-03-01 Kathryn A. F. Pennel, Phimmada Hatthakarnkul, Colin S. Wood, Guang-Yu Lian, Sara S. F. Al-Badran, Jean A. Quinn, Assya Legrini, Jitwadee Inthagard, Peter G. Alexander, Hester van Wyk, Ahmad Kurniawan, Umar Hashmi, Michael A. Gillespie, Megan Mills, Aula Ammar, Jennifer Hay, Ditte Andersen, Colin Nixon, Selma Rebus, David K. Chang, Caroline Kelly, Andrea Harkin, Janet Graham, David Church, Ian Tomlinson
Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and
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IL6-STAT3-C/EBPβ-IL6 positive feedback loop in tumor-associated macrophages promotes the EMT and metastasis of lung adenocarcinoma J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-02-29 Zhengyang Hu, Qihai Sui, Xing Jin, Guangyao Shan, Yiwei Huang, Yanjun Yi, Dejun Zeng, Mengnan Zhao, Cheng Zhan, Qun Wang, Zongwu Lin, Tao Lu, Zhencong Chen
Lung cancer is one of the most common tumors in the world, and metastasis is one of the major causes of tumor-related death in lung cancer patients. Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and are frequently associated with tumor metastasis in human cancers. However, the regulatory mechanisms of TAMs in lung cancer metastasis remain unclear. Single-cell
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ThermomiR-377-3p-induced suppression of Cirbp expression is required for effective elimination of cancer cells and cancer stem-like cells by hyperthermia J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-02-29 Tao-Yan Lin, Jun-Shuang Jia, Wei-Ren Luo, Xiao-Lin Lin, Sheng-Jun Xiao, Jie Yang, Jia-Wei Xia, Chen Zhou, Zhi-Hao Zhou, Shu-Jun Lin, Qi-Wen Li, Zhi-Zhi Yang, Ye Lei, Wen-Qing Yang, Hong-Fen Shen, Shi-Hao Huang, Sheng-Chun Wang, Lin-Bei Chen, Yu-Lin Yang, Shu-Wen Xue, Yong-Long Li, Guan-Qi Dai, Ying Zhou, Ying-Chun Li, Fang Wei, Xiao-Xiang Rong, Xiao-Jun Luo, Bing-Xia Zhao, Wen-Hua Huang, Dong Xiao
In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC)
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Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-02-27 Lidwien P. Smabers, Emerens Wensink, Carla S. Verissimo, Esmee Koedoot, Katerina-Chara Pitsa, Maarten A. Huismans, Celia Higuera Barón, Mayke Doorn, Liselot B. Valkenburg-van Iersel, Geert A. Cirkel, Anneta Brousali, René Overmeer, Miriam Koopman, Manon N. Braat, Bas Penning de Vries, Sjoerd G. Elias, Robert G. Vries, Onno Kranenburg, Sylvia F. Boj, Jeanine M. Roodhart
The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard
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Targeting HDAC6 improves anti-CD47 immunotherapy J. Exp. Clin. Cancer Res. (IF 11.3) Pub Date : 2024-02-27 Maria Gracia-Hernandez, Ashutosh S. Yende, Nithya Gajendran, Zubaydah Alahmadi, Xintang Li, Zuleima Munoz, Karen Tan, Satish Noonepalle, Maho Shibata, Alejandro Villagra
Cancer cells can overexpress CD47, an innate immune checkpoint that prevents phagocytosis upon interaction with signal regulatory protein alpha (SIRPα) expressed in macrophages and other myeloid cells. Several clinical trials have reported that CD47 blockade reduces tumor growth in hematological malignancies. However, CD47 blockade has shown modest results in solid tumors, including melanoma. Our group