Inhibiting the inhibitors: evaluating agents targeting cancer immunosuppression

Importance of the field: Immunotherapy of cancer has not improved disease-free or overall patient survival. The lack of concordance between immunological and clinical responses in cancer immunotherapy trials is thought to result from the pervasive presence of tumor-driven immune suppression that allows tumor to escape and that has not been adequately targeted by current therapies. Areas covered in this review: Because multiple mechanisms of tumor induced suppression have been identified and shown to contribute to tumor escape, the opportunity arises to interfere with these mechanisms. A range of known tumor-derived inhibitors can now be blocked or neutralized by biologic or metabolic agents. Used alone or in combination with each other or with conventional cancer therapies, these agents offer novel therapeutic strategies for the control of tumor escape. What the reader will gain: This review deals with currently available inhibitors for counteracting tumor immune escape. The restoration of effective antitumor immunity in patients with cancer will require new approaches aiming at: i) protection of immune cells from adverse effects of myeloid-derived suppressor cells, regulatory T cells or inhibitory factors thus enhancing effector functions; and ii) prolonging survival of central memory T cells, thus ensuring long-term protection. Take home message: Inhibitors of mechanisms responsible for tumor escape could restore anti-tumor immune responses in patients with cancer.