Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Cancer Cell. 2022 May 9;40(5):479-493.e6. doi: 10.1016/j.ccell.2022.03.012. Epub 2022 Apr 21.
A common theme across multiple successful immunotherapies for cancer is the recognition of tumor-specific mutations (neoantigens) by T cells. The rapid discovery of such antigen responses could lead to improved therapies through the adoptive transfer of T cells engineered to express neoantigen-reactive T cell receptors (TCRs). Here, through CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TILs), we develop a neoantigen-reactive T cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. Screening of TCRs selected by the signature allows us to identify neoantigen-reactive TCRs with a success rate of 45% for CD8 and 66% for CD4 T cells. Because of the small number of samples analyzed (4 patients), generalizability remains to be tested. However, this approach can enable the quick identification of neoantigen-reactive TCRs and expedite the engineering of personalized neoantigen-reactive T cells for therapy.
多种癌症免疫疗法的一个共同主题是 T 细胞识别肿瘤特异性突变（新抗原）。快速发现这种抗原反应可能会通过过继转移表达新抗原反应性 T 细胞受体（TCR）的 T 细胞来改善治疗方法。在这里，通过 CITE-seq（通过测序对转录组和表位进行细胞索引）和非小细胞肺癌（NSCLC）肿瘤浸润淋巴细胞（TIL）的 TCR-seq，我们基于克隆型频率以及 CD39 蛋白和 CXCL13 mRNA 表达开发了一个新抗原反应性 T 细胞特征。对特征选择的 TCR 进行筛选，使我们能够识别新抗原反应性 TCR，CD8 T 细胞的成功率为 45%，CD4 T 细胞的成功率为 66%。由于分析的样本数量较少（4 例），因此仍有待验证其普遍性。然而，这种方法可以快速识别新抗原反应性 TCR，并加快个性化新抗原反应性 T 细胞的工程化用于治疗。
