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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Cancer Immunology, Immunotherapy ( IF 5.8 ) Pub Date : 2024-04-17 , DOI: 10.1007/s00262-024-03691-9
Sangjoon Choi , Mofazzal Hossain , Hyun Lee , Jina Baek , Hye Seon Park , Chae-Lyul Lim , DoYeon Han , Taehyun Park , Jong Hyeok Kim , Gyungyub Gong , Mi-Na Kweon , Hee Jin Lee

Background

Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes.

Methods

TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1–2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion.

Results

TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases.

Conclusion

We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.



中文翻译:

扩增来自头颈鳞状细胞癌的肿瘤浸润淋巴细胞以评估过继细胞疗法的潜力

背景

体外扩增的肿瘤浸润淋巴细胞(TIL)的过继转移可有效消退几种类型的恶性肿瘤。本研究评估了头颈鳞状细胞癌 (HNSCC) 中肿瘤浸润淋巴细胞 (TIL) 的产量和影响成功扩增的因素及其免疫表型。

方法

TIL 是从 47 个手术切除的 HNSCC 标本及其转移淋巴结中扩增出来的。将癌组织切成小块(1-2毫米)并进行2周的初步扩张。检查肿瘤位置、吸烟史、间质 TIL 百分比、人乳头瘤病毒感染和程序性死亡配体 1 评分对 TIL 成功扩增的影响。使用荧光激活细胞分选通过流式细胞术评估扩增的 TIL。在快速扩增方案之后,对成功 TIL 扩增的样本子集进行了第二轮 TIL 扩增。

结果

TIL 已从 36.2% 的样本中成功扩增。失败的原因是污染(27.6%)或膨胀不足(36.2%)。只有基质 TIL 百分比与成功的 TIL 扩张显着相关 ( p  = 0.032)。基质 TIL 百分比还显示与每个片段扩展的 TIL 相关(r  = 0.341,p  = 0.048)。对 13 个 TIL 扩增成功的样本进行流式细胞术分析,发现 69.2% 的病例中 CD4 + T 细胞占优势。在所有病例中,效应记忆 T 细胞是扩增的 CD4 + 和 CD8 + T 细胞的主要表型。

结论

我们可以从大约三分之一的 HNSCC 样本中扩展 TIL。 TIL 扩展可适用于具有不同临床病理特征的 HNSCC 样本。

更新日期:2024-04-18
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