Background

Immunotherapy is now seen as a potential remedy for colorectal cancer (CRC). Chemokines play a crucial role in tumors, including CRC, which contains CXCL1. We attempted to study how CXCL1 impacts immune escape in CRC.

Methods

Bioinformatics analysis was used to examine CXCL1 level in CRC. qRT-PCR was used to assess CXCL1 and MHC-I (HLA-A, B, C) levels. Cell Counting Kit-8 (CCK-8) was used to measure cell viability. Cytotoxicity assay kit was utilized to assay CD8⁺ T cell cytotoxicity against CRC. Flow cytometry tested proliferation and apoptosis of CD8⁺ T cells. Chemotaxis assay evaluated chemotaxis of CD8⁺ T cells towards CRC. Immunofluorescence examined expression of autophagy marker LC3 and localization of NBR1/MHC-I. Western blot analysis measured protein levels of chemokines CXCL9 and CXCL10, autophagy-related proteins LC3-I and LC3-II, and MHC-I (HLA-A, B, C).

Results

Bioinformatics analysis and qRT-PCR presented that CXCL1 was upregulated in CRC. Cell experiments demonstrated that CXCL1 overexpression promoted immune escape in CRC. Rescue experiments revealed that the autophagy inducer Rapa could attenuate the inhibitory effect of CXCL1 low expression on immune escape in CRC. Further studies showed that CXCL1 promoted immune escape in CRC by autophagy-mediated MHC-I degradation.

Conclusion

CXCL1 promoted immune escape in CRC by autophagy-mediated MHC-I degradation, suggesting that CXCL1 may be a possible immunotherapeutic target for CRC.

中文翻译：

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CXCL1通过自噬介导的MHC-I降解促进结直肠癌的免疫逃逸

背景

免疫疗法现在被视为结直肠癌（CRC）的潜在治疗方法。趋化因子在肿瘤中发挥着至关重要的作用，包括包含 CXCL1 的 CRC。我们试图研究 CXCL1 如何影响CRC 的免疫逃逸。

方法

使用生物信息学分析来检查 CRC 中的 CXCL1 水平。qRT-PCR 用于评估 CXCL1 和 MHC-I（HLA-A、B、C）水平。使用细胞计数试剂盒-8 (CCK-8) 测量细胞活力。使用细胞毒性测定试剂盒测定CD8 ⁺ T细胞对CRC的细胞毒性。流式细胞术检测CD8 ⁺ T细胞的增殖和凋亡。趋化性测定评估了 CD8 ⁺ T 细胞对 CRC 的趋化性。免疫荧光检查自噬标记物 LC3 的表达和 NBR1/MHC-I 的定位。蛋白质印迹分析测量趋化因子 CXCL9 和 CXCL10、自噬相关蛋白 LC3-I 和 LC3-II 以及 MHC-I (HLA-A、B、C) 的蛋白水平。

结果

生物信息学分析和qRT-PCR表明CXCL1在结直肠癌中表达上调。细胞实验表明，CXCL1 过度表达促进了 CRC 的免疫逃逸。拯救实验表明，自噬诱导剂Rapa可以减弱CXCL1低表达对CRC免疫逃逸的抑制作用。进一步的研究表明，CXCL1 通过自噬介导的 MHC-I 降解促进 CRC 的免疫逃逸。

结论

CXCL1通过自噬介导的MHC-I降解促进CRC的免疫逃逸，这表明CXCL1可能是CRC的一个可能的免疫治疗靶点。