过继转移的肿瘤特异性产 IL-9 细胞毒性 CD8(+) T 细胞激活宿主 CD4(+) T 细胞以控制抗原丢失的肿瘤

Host effector CD4 + T cells emerge as critical mediators for tumor regression but whether they can be activated by adoptively transferred CD8 + T cells remains unknown.

We previously reported that adoptive transfer of interleukin 9 (IL-9)-producing cytotoxic CD8 + T (Tc9) cells achieved long-term control of tumor growth.

Here, we demonstrate that murine tumor-specific Tc9 cells control the outgrowth of antigen-loss relapsed tumors by recruiting and activating host effector CD4 + T cells. Tc9 cells secreted IL-24 and recruited CCR7-expressing conventional type 2 dendritic cells (cDC2 cells) into tumor-draining lymph nodes to prime host CD4 + T cells against relapsed tumors. Host CD4 + T cell or cDC2 deficiency impaired the ability of Tc9 cells to control relapsed tumor outgrowth.

Additionally, intratumoral IL24 expression correlates with cDC2 and CD4 + T cell gene signatures in human cancers and their expression is associated with better patient survival.

This study reports a mechanism for activation of tumor-specific CD4 + T cells in vivo.