美国普罗维登斯癌症研究院Eric Tran和郑春红研究组，揭示了人胃肠肿瘤细胞中新抗原反应性T细胞的转录组学特征。相关论文发表在2022年4月11日出版的《癌细胞》杂志上。

研究人员对来自胆管和胰腺癌患者的肿瘤浸润性淋巴细胞进行了靶向个性化新抗原的免疫筛查，并结合单细胞RNA测序来表征新抗原反应性T细胞的转录组学特征。研究发现，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细胞表现出耗竭状态，CXCL13和GZMA共表达显著。胆管癌患者的大多数新抗原反应性CD4⁺ T细胞也表现出耗竭的表型，但具有HOPX或ADGRG1过表达而IL7R表达缺乏的特征。因此，胃肠癌浸润性新抗原反应性T细胞具有不同的转录组特征，这为利用这些细胞进行治疗提供了新机会。

据介绍，肿瘤浸润性新抗原反应性T细胞有利于介导转移性胃肠癌的消退，但其特征仍然未知。

附：英文原文

Title: Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers

Author: Chunhong Zheng, Joseph N. Fass, Yi-Ping Shih, Andrew J. Gunderson, Nelson Sanjuan Silva, Huayu Huang, Brady M. Bernard, Venkatesh Rajamanickam, Joseph Slagel, Carlo B. Bifulco, Brian Piening, Pippa H.A. Newell, Paul D. Hansen, Eric Tran

Issue&Volume: 2022/04/11

Abstract: Tumor-infiltrating neoantigen-reactive T cells can mediate regression of metastaticgastrointestinal cancers yet remain poorly characterized. We performed immunologicalscreening against personalized neoantigens in combination with single-cell RNA sequencingon tumor-infiltrating lymphocytes from bile duct and pancreatic cancer patients tocharacterize the transcriptomic landscape of neoantigen-reactive T cells. We foundthat 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-reactiveCD4+ T cells from a patient with bile duct cancer also exhibited an exhausted phenotypebut with overexpression of HOPX or ADGRG1 while lacking IL7R expression. Thus, neoantigen-reactive T cells infiltrating gastrointestinal cancersharbor distinct transcriptomic signatures, which may provide new opportunities forharnessing these cells for therapy.

DOI: 10.1016/j.ccell.2022.03.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00120-9