Targeted Therapy and Immunosuppression in the Tumor Microenvironment

Small-molecule inhibitors offer great promise for targeting pathways that are specifically deregulated in different tumors. However, such 'targeted' therapies also elicit poorly understood effects on protective antitumor immunity. Given the emerging relevance of immunotherapies that boost pre-existing T cell responses, understanding how different immune cells are affected by small-molecule inhibitors could lead to more-effective interventions, alone or combined with immunotherapy. This review discusses the growing array of activities elicited by multiple 'targeted' inhibitors on antitumor immunity, underscoring the complex effects resulting from diverse activities on different immune cell types in vivo, and the need to conduct mechanistic research that identifies drugs performing well not only in immunocompromised mice but also in the presence of spontaneous or therapeutic antitumor immunity.