Figure 4. Model of TGFβ-mediated inhibition of antitumor T cell response. In the tumor-draining lymph nodes, CD4⁺ T cells become activated in response to tumor-associated antigens. Activated CD4⁺ T cells in the tumor draining lymph nodes secrete TGFβ1 that suppresses the activation, proliferation and differentiation of naïve tumor-specific CD8⁺ T cells into IFNγ-secreting T cells. Consequently, activated CD8⁺ T cells that migrate to the tumor site as effectors fail to elaborate CTL functions including GzmB expression. In addition, effector CD4⁺ T cells at the tumor site might also produce TGFβ1 to suppress the effector activities of CD8⁺ T cells. The net result is CTL dysfunction, which allows tumors to grow.