Abstract
The immune system is a vital determinant of cancer and shapes its trajectory. Notably, the immune reaction to cancer harbors dual potential for suppressing or promoting cancer development and progression. This polarity of the immune response is determined, in part, by the character of the interplay between innate and adaptive immunity. On the one hand, the innate immune compartment is a necessary proponent of cancer immunity by supporting an immunostimulatory state that enables T cell immunosurveillance. However, in the setting of cancer, innate immune cells are commonly polarized with immune-suppressive properties and as a result, orchestrate a tolerogenic niche that interferes with the cytotoxic potential of tumor antigen-specific T cells. Here, we discuss the role of innate immunity as a positive and negative regulator of adaptive immunosurveillance; moreover, we highlight how tumor cells may skew leukocytes toward an immunosuppressive state and, as such, subvert the phenotypic plasticity of the immune compartment to advance disease progression. These observations establish the precedent for novel therapeutic strategies that aim to restore the tumor microenvironment to an immunoreactive state and, in doing so, condition and maintain the immunogenicity of tumors to yield deep and durable responses to immunotherapy.