Innate Immune Signaling in Regulation of Immunity

Innate resistance, as an integral part of inflammation, and adaptive immunity participate in oncogenesis and tumor surveillance. For a long time, innate resistance was considered a primitive nonspecific form of resistance to infections that was eclipsed by the potent and specific acquired immunity of higher organisms. More recently, it has been recognized that innate resistance is not only the first line of defense against infections but also sets the stage and is necessary for the development of adaptive immunity. Advances in cancer biology have revealed that the defensive mechanisms of innate resistance and inflammation are indeed manifestations of tissue homeostasis and control of cellular proliferation that have many pleiotropic effects on carcinogenesis and tumor progression and dissemination. The interaction of innate and adaptive immunity with carcinogenesis and tumor progression is complicated and results in effects that either favor or impede tumor progression. Innate immune receptors both sense and regulate the composition of the microbiota, the large number of commensal microorganisms that colonize the barrier surfaces of all multicellular organisms, including those of humans. The microbiota affects many functions of our body and the two together comprise one metaorganism. Microbial imbalance particularly in the gut plays a critical role in the development of multiple diseases, such as cancer, autoimmune conditions and increased susceptibility to infection. Alteration in innate immune signaling and immunity may change the composition of the microbiota affecting tumor initiation both at the barrier sites (e.g. in the gut) and systemically. The commensal microbes not only may affect the development and progression of cancer but they have also important effects on the response to cancer therapy. Mostly through their interaction with innate receptors, commensal microorganisms modulate the ability of the organism to respond to cancer immunotherapy and chemotherapy by affecting the threshold of response of tumor-associated myeloid cells and their ability to sustain anti-tumor immunity.