Cancer Immunology and Immunotherapy

The interplay between tumors and their immunologic microenvironment is complex, difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. The present review discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Current active immunotherapy trials have shown durable tumor regressions in a fraction of patients. However, clinical efficacy of current vaccines is limited, possibly because tumors skew the immune system by means of myeloid-derived suppressor cells, inflammatory type 2 T cells and regulatory T cells (Tregs), all of which prevent the generation of effector cells. To improve the clinical efficacy of cancer vaccines in patients with metastatic disease, we need to design novel and improved strategies that can boost adaptive immunity to cancer, help overcome Tregs and allow the breakdown of the immunosuppressive tumor microenvironment.

The recent FDA approval of Provenge® as the first therapeutic cancer vaccine together with the recent demonstration that Ipilimumab®, a monoclonal antibody that blocks the negative immune checkpoint cytotoxic T lymphocyte associated antigen-4, prolongs patient survival are major achievements that usher in a new era of cancer immunotherapy. These “first-in-class” treatments reflect the substantive progress that basic and translational scientists have made towards understanding the mechanisms underlying protective tumor immunity in cancer patients Immunotherapies were first explored at the turn of the twentieth century, but the crafting of potent treatments required more detailed knowledge of how the immune system responds to cancer. Advances in genetic, cellular, and biochemical technologies have begun to yield this critical information, focusing attention on immune recognition, regulation, and escape. Indeed, the dynamic interplay of these processes in the tumor microenvironment is now recognized to play a decisive role in determining disease outcome. This volume highlights the rapid progress and breadth of research in cancer immunology, and provides a framework for anticipating many more clinical successes in cancer immunotherapy.