%0 Journal Article
%T IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy.
%A Lee KJ
%A Choi D
%A Tae N
%A Song HW
%A Kang YW
%A Lee M
%A Moon D
%A Oh Y
%A Park S
%A Kim JH
%A Jeong S
%A Yang J
%A Park U
%A Hong DH
%A Byun MS
%A Park SH
%A Sohn J
%A Park Y
%A Im SK
%A Choi SS
%A Kim DH
%A Lee SW
%J Cell Rep Med
%V 5
%N 5
%D 2024 May 21
%M 38744277
%F 16.988
%R 10.1016/j.xcrm.2024.101567
%X 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-7-hyFc-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.