Tumor-infiltrating human CD4+ regulatory T cells display a distinct TCR repertoire and exhibit tumor and neoantigen reactivity

摘要: CD4+ regulatory T (Treg) cells have an essential function in maintaining self-tolerance; however, they may also play a detrimental role antitumor immune responses. The presence of elevated frequencies Treg tumors correlates with disease progression and poor survival patients cancer. antigen specificity that expanded the tumor microenvironment is poorly understood; answering this question provide important insights for immunotherapeutic approaches. To address this, we used novel combinatorial approach to characterizing cell receptor (TCR) profiles intratumoral from metastatic melanoma, gastrointestinal, ovarian cancers elucidated their specificities. TCR repertoires tumor-resident were diverse yet displayed significant overlap circulating but not conventional or blood. TCRs isolated specific reactivity against autologous mutated neoantigens, suggesting act antigen–selective manner leading activation clonal expansion microenvironment. Tumor antigen–specific Treg-derived resided circulation, both compartments serve as source tumor-specific TCRs. These findings into tumor-infiltrating human potential implications cancer immunotherapy.