Xiao et al. demonstrated that adoptively transferred Tc9 cells (IL-9-producing cytotoxic CD8+ T cells) were able to control the growth of B16-OVA tumors, even upon antigen loss. Investigating the mechanism, they found that Tc9 cell secretion of IL-24 recruited CCR7+ cDC2s to tumors. These cDC2s migrated to tdLNs, where they primed host cytotoxic effector CD4+ T cells, which then infiltrated tumors and contributed to tumor growth control. In patient data for melanoma and breast cancer, intratumoral IL24 expression correlated with cDC2 and CD4+ T cell signatures, which were both associated with longer survival.
Contributed by Lauren Hitchings
ABSTRACT: 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.
