Enhancing T cell performance against cancer in combination treatment strategies

Increasing evidence suggests that some patients with cancer can mount an antitumor immune response capable of controlling cancer. Although both innate (natural killer cells, dendritic cells) and adaptive (T cells) immunity play important roles in cancer immune surveillance, most emphasis has been placed on the exploitation of adaptive immune responses for cancer immunotherapy. In particular, several preclinical and clinical reports have shown that both cytotoxic CD8+ T cells (CTLs) and CD4+ Th1 cells are able to control and even completely reject tumors through the secretion of cytokines such as interferon gamma (IFN-γ) and tumor necrosis factor alfa (TNF-α). These observations have spurred a revolution in cancer therapeutics, as several treatment strategies are clinically tested and developed in an iterative fashion. In melanoma, multiple immunotherapeutic approaches aimed at manipulating and optimizing the activation of CTLs and CD4+ Th1 cells and their recruitment to malignant tissue are being assessed. Here, we provide an overview of the main immune-oncology treatment strategies that, either alone or in combination, are undergoing clinical development at different stages. Namely, we will refer to those immunotherapeutic strategies that include cancer vaccines, adoptive transfer of ex vivo activated T cells and immunomodulatory monoclonal antibodies.