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A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers

2022; Cell Press; Volume: 40; Issue: 5 Linguagem: Inglês

10.1016/j.ccell.2022.03.012

1878-3686

Ken‐ichi Hanada, Chihao Zhao, Raúl Gil-Hoyos, Jared J. Gartner, Christopher A. Chow, Frank J. Lowery, Sri Krishna, Todd D. Prickett, Scott Kivitz, Maria R. Parkhurst, Nathan Wong, Zachary Rae, Michael C. Kelly, Stephanie L. Goff, Paul F. Robbins, Steven A. Rosenberg, James C. Yang,

CAR-T cell therapy research

Summary 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.