CD4⁺ anti-TGF-β CAR T cells and CD8⁺ conventional CAR T cells exhibit synergistic antitumor effects.

ABSTRACT: Transforming growth factor (TGF)-β1 restricts the expansion, survival, and function of CD4⁺ T cells. Here, we demonstrate that CD4⁺ but not CD8⁺ anti-TGF-β CAR T cells (T28zT2 T cells) can suppress tumor growth partly through secreting Granzyme B and interferon (IFN)-γ. TGF-β1-treated CD4⁺ T28zT2 T cells persist well in peripheral blood and tumors, maintain their mitochondrial form and function, and do not cause in vivo toxicity. They also improve the expansion and persistence of untransduced CD8⁺ T cells in vivo. Tumor-infiltrating CD4⁺ T28zT2 T cells are enriched with TCF-1⁺IL7R⁺ memory-like T cells, express NKG2D, and downregulate T cell exhaustion markers, including PD-1 and LAG3. Importantly, a com

SUBMITTER: Zheng D 

PROVIDER: S-EPMC11970399 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature