肿瘤细胞治疗研究
英文原题：Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers.
Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers.
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肿瘤浸润性新抗原反应性 T 细胞能够介导转移性胃肠道肿瘤的消退，但目前对其特征仍了解不足。
肿瘤浸润性新抗原反应性T细胞能够介导转移性胃肠道肿瘤的消退，但目前对其特征仍认识不足。我们对胆管癌和胰腺癌患者的TIL（肿瘤浸润淋巴细胞）进行了针对个体化新抗原的免疫筛选，并结合单细胞RNA测序，以描绘新抗原反应性T细胞的转录组图谱。我们发现，与非新抗原反应性旁观者细胞相比，大多数新抗原反应性CD8+ T细胞呈现耗竭状态，并具有显著的CXCL13和GZMA共表达。来自一名胆管癌患者的大多数新抗原反应性CD4+ T细胞也表现出耗竭表型，但伴有HOPX或ADGRG1过表达，同时缺乏IL7R表达。因此，浸润胃肠道肿瘤的新抗原反应性T细胞具有独特的转录组特征，这可能为利用这些细胞进行治疗提供新的机会。
Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastatic gastrointestinal cancers yet remain poorly characterized. We performed immunological screening against personalized neoantigens in combination with single-cell RNA sequencing on tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients to characterize the transcriptomic landscape of neoantigen-reactive T cells. We found that most neoantigen-reactive CD8 + T cells displayed an exhausted state with significant CXCL13 and GZMA co-expression compared with non-neoantigen-reactive bystander cells. Most neoantigen-reactive CD4 + T cells from a patient with bile duct cancer also exhibited an exhausted phenotype but with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancers harbor distinct transcriptomic signatures, which may provide new opportunities for harnessing these cells for therapy.
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