| First Author | Lee KJ | Year | 2024 |
| Journal | Cell Rep Med | Volume | 5 |
| Issue | 5 | Pages | 101567 |
| PubMed ID | 38744277 | Mgi Jnum | J:352099 |
| Mgi Id | MGI:7704227 | Doi | 10.1016/j.xcrm.2024.101567 |
| Citation | Lee KJ, et al. (2024) IL-7-primed bystander CD8 tumor-infiltrating lymphocytes optimize the antitumor efficacy of T cell engager immunotherapy. Cell Rep Med 5(5):101567 |
| abstractText | 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. |
