IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy

Abstract

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL -7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor -infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD -1 -negative tumor non -responsive bystander T cells. However, they are non -exhausted and central memory -phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen -specific TCEs to acquire tumoricidal activity. Single -cell transcriptome analysis reveals that rhIL-7hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor -reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.