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.
Author Info: (1) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. xiaoliuling@cqmu.edu.cn. First Affiliated Hospital, School of Basic Medicine, Chon
Author Info: (1) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. xiaoliuling@cqmu.edu.cn. First Affiliated Hospital, School of Basic Medicine, Chongqing Medical University, Chongqing, China. xiaoliuling@cqmu.edu.cn. (2) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (3) The University of Texas MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA. (4) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (5) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (6) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (7) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (8) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (9) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (10) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (11) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (12) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (13) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (14) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (15) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. (16) The University of Texas MD Anderson Cancer Center, UTHealth Houston Graduate School of Biomedical Sciences, Houston, TX, USA. Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA. Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA. (17) Houston Methodist Neal Cancer Center, Houston Methodist Research Institute, Houston, TX, USA. qyi@houstonmethodist.org.
