Innate immune cells participate in the detection of tumor cells via complex signaling pathways mediated by pattern-recognition receptors, such as Toll-like receptors and nucleotide-binding and oligomerization domain-like receptors. These pathways are finely tuned via multiple mechanisms, including epigenetic regulation. It is well established that hematopoietic progenitors generate innate immune cells that can regulate cancer cell behavior, and the disruption of normal hematopoiesis in pathologic states may lead to altered immunity and the development of cancer. In this review, we discuss the epigenetic and transcriptional mechanisms that underlie the initiation and amplification of innate immune signaling in cancer. We also discuss new targeting possibilities for cancer control that exploit innate immune cells and signaling molecules, potentially heralding the next generation of immunotherapy.
©2022 The Authors; Published by the American Association for Cancer Research.