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.

多种成功的癌症免疫疗法的一个共同主题是 T 细胞对肿瘤特异性突变（新抗原）的识别。这种抗原反应的快速发现可能会通过过继转移经过改造的 T 细胞来表达新抗原反应性 T 细胞受体 (TCR)，从而改进治疗方法。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，我们开发了基于克隆型的新抗原反应性 T 细胞特征频率以及 CD39 蛋白和CXCL13 mRNA 表达。通过签名选择的 TCR 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 名患者），普遍性仍有待测试。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 细胞的工程设计以用于治疗。