Tumor-specific IL-9–producing CD8+ Tc9 cells are superior effector than type-I cytotoxic Tc1 cells for adoptive immunotherapy of cancers

Y Lu, B Hong, H Li, Y Zheng, M Zhang, S Wang… - Proceedings of the …, 2014 - pnas.org
Y Lu, B Hong, H Li, Y Zheng, M Zhang, S Wang, J Qian, Q Yi
Proceedings of the National Academy of Sciences, 2014pnas.org
Because cytokine-priming signals direct CD8+ T cells to acquire unique profiles that affect
their ability to mediate specific immune responses, here we generated IL-9–skewed CD8+ T
(Tc9) cells by priming with Th9-polarized condition. Compared with type-I CD8+ cytotoxic T
(Tc1) cells, Tc9 secreted different cytokines and were less cytolytic in vitro but surprisingly
elicited greater antitumor responses against advanced tumors in OT-I/B16-OVA and Pmel-
1/B16 melanoma models. After adoptive transfer, Tc9 cells persisted longer and …
Because cytokine-priming signals direct CD8+ T cells to acquire unique profiles that affect their ability to mediate specific immune responses, here we generated IL-9–skewed CD8+ T (Tc9) cells by priming with Th9-polarized condition. Compared with type-I CD8+ cytotoxic T (Tc1) cells, Tc9 secreted different cytokines and were less cytolytic in vitro but surprisingly elicited greater antitumor responses against advanced tumors in OT-I/B16-OVA and Pmel-1/B16 melanoma models. After adoptive transfer, Tc9 cells persisted longer and differentiated into IFN-γ– and granzyme-B (GrzB)–producing cytolytic Tc1-like effector cells. Phenotypic analysis revealed that adoptively transferred Tc9 cells secreted IL-2 and were KLRG-1low and IL-7Rαhigh, suggesting that they acquired a signature of “younger” phenotype or became long-term lived cells with capacity of self-renewal. Our results also revealed that Tc9-mediated therapeutic effect critically depended on IL-9 production in vivo. These findings have clinical implications for the improvement of CD8+ T-cell-based adoptive immunotherapy of cancers.
pnas.org