Requirement of Innate Immunity in Tumor-Bearing Mice Cured by Adoptive Immunotherapy Using Tumor-Draining Lymph Nodes
Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine ‘sinks’ for homeostatic γC-cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4+CD25+ regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.