Most
tumors employ multiple strategies to attenuate T-cell-mediated immune responses. In particular, immune suppression surrounding the
tumor is achieved by interfering with antigen-presenting cells and effector T cells. Controlling both the
tumor and the tumor microenvironment (TME) is critical for
cancer treatment. Checkpoint blockade
therapy can overcome
tumor-induced immune suppression, but more than half of the patients fail to respond to this treatment; therefore, more effective
cancer immunotherapies are needed. Generation of an anti-
tumor immune response is a multi-step process of immune activation against the
tumor that requires effector T cells to recognize and exert toxic effects against
tumor cells, for which two strategies are employed-inhibition of various types of immune suppressor cells, such as myeloid cells and regulatory T cells, and establishment of anti-
tumor immune surveillance including, activation of natural killer cells and cytotoxic T cells. It was recently shown that anti-
cancer drugs not only directly kill
tumor cells, but also influence the immune response to
cancer by promoting immunogenic cell death, enhancing antigen presentation or depleting immunosuppressive cells. Herein, we review the mechanisms by which
tumors exert immune suppression as well as their regulation. We then discuss how the complex reciprocal interactions between immunosuppressive and immunostimulatory cells influence immune cell dynamics in the TME. Finally, we highlight the new
therapies that can reverse immune suppression in the TME and promote anti-
tumor immunity.