Using two tumor models in a TCRα repertoire-deficient mouse strain, Zhang et al. found that transfer of wild-type thymocytes or splenocytes prior to tumor injection resulted in inhibition of s.c. tumor growth, reduction in lung metastases, and prolonged survival. Experiments using transfer of purified cell populations, depleting antibodies, and combinations of KO strains established that antitumor effects were initiated by IFNγ+CXCR6+ CD4+ TRM cells of donor origin, and also required IFNγ-producing NK cells of endogenous origin. Cell transfer dramatically altered the TME, leading to decreased MDSCs, increased TAMs, and elevated T cell chemoattractants.
Contributed by Margot O’Toole
ABSTRACT: Tumor immunology has been studied extensively. Tumor immunology-based cancer immunotherapy has become one of the most promising approaches for cancer treatment. However, one of the fundamental aspects of tumor immunology-the initiation of antitumor immunity-is not fully understood. Compared to that of CD8+ T cells, the effect of CD4+ T cells on antitumor immunity has not been fully appreciated. Using a gene knockout mouse model, the mice of which are deficient in the TCRα repertoire, specifically lacking invariant NKT and mucosal-associated invariant T cells, we found that the deficiency in TCRα repertoire diversity did not affect the antitumor immunity, at least to B16BL6 melanoma and EO771 breast cancer. However, after acquiring thymocytes or splenocytes from wild-type mice, these knockout mice exhibited greatly enhanced and long-lasting antitumor immunity. This enhanced antitumor immunity depended on CD4+ T cells, especially CD4+ tissue-resident memory T (TRM) cells, but not invariant NKT or CD8+ T cells. We also present evidence that CD4+ TRM cells initiate antitumor immunity through IFN-γ, and the process is dependent on NK cells. The CD4+ TRM/NK axis appears to control tumor formation and development by eliminating tumor cells and modulating the tumor microenvironment. Taken together, our results demonstrated that CD4+ TRM cells play a dominant role in the initiation of antitumor immunity.
Author Info: (1) Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA hzhang@wsu.edu. (2) Department of Pharmaceutica
Author Info: (1) Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA hzhang@wsu.edu. (2) Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA. (3) Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA. (4) Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA.
