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

Bispecific T-cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors with immunosuppressive environments remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, allowing TCE-immunotherapy to function effectively in solid tumors. In order to explore the transcriptomic changes induced by rhIL-7-hyFc or a combination of rhIL-7-hyFc and TCE treatment at the clonal level, we performed scRNA/TCR-seq. Overall design: Tumor-infiltrating CD8 T cells from mice bearing MC38 tumors were isolated following two treatment conditions: (1) treatment with either buffer or rhIL-7-hyFc, and (2) treatment with either rhIL-7-hyFc or a combination of rhIL-7-hyFc and TCE. For the enrichment of CD8 T cells, cells were isolated by positive selection methods with IMag (condition 1) or sorted by FACS (condition 2) after single-cell preparation. The purified CD8 T cells were analyzed by scRNA-seq paired with scTCR-seq.