TGFβ suppresses CD8⁺ T cell expression of CXCR3 and tumor trafficking.

ABSTRACT: Transforming growth factor beta (TGFβ) is a multipotent immunosuppressive cytokine. TGFβ excludes immune cells from tumors, and TGFβ inhibition improves the efficacy of cytotoxic and immune therapies. Using preclinical colorectal cancer models in cell type-conditional TGFβ receptor I (ALK5) knockout mice, we interrogate this mechanism. Tumor growth delay and radiation response are unchanged in animals with Treg or macrophage-specific ALK5 deletion. However, CD8αCre-ALK5^flox/flox (ALK5^ΔCD8) mice reject tumors in high proportions, dependent on CD8⁺ T cells. ALK5^ΔCD8 mice have more tumor-infiltrating effector CD8⁺ T cells, with more cytotoxic capacity. ALK5-deficient CD8⁺ T cells exhibit increased CXCR3 expression and enhanced

SUBMITTER: Gunderson AJ 

PROVIDER: S-EPMC7145847 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature