Cd40l(+) Cd8(+) T-Cell Dependent Antitumor Immunity

CD40 is frequently expressed on malignant cells of different origin. Due to the observed antitumorigenic effects induced after CD40 engagement it represents an attractive target for immunotherapies. We demonstrate here that CD40L expressing tumor-specific CD8+ T-cell population can act as potent physiological CD40 agonist against CD40 expressing tumor cells. We demonstrate that in the course of cancer cell rejection high frequencies of tumor-specific CD40L+ CD8+ T cells are induced. Strikingly, in contrast to wild-type (wt), CD40L deficient CD8+ T cells were unable to prevent tumor formation in lymphopenic as well as in fully immunocompetent hosts. Apparently, in our setting CD40L expressed by CD8+ T cells is essential for cancer cell rejection. CD40L-mediated rejection does not depend on interaction with CD40+ host cells such as antigen-presenting cells but on CD40 expression by cancer cells. Our findings disclose CD40L expression by CD8+ T cells as a new antitumor effector function that should be implemented in future adoptive T-cell therapies against cancer.