Epigenetic Reprogramming of Erythroid Progenitor Cells: Insights for Enhancing Cancer Immunotherapy

Cancer immunotherapy has markedly improved clinical outcomes for cancer patients. However, its broad application is constrained by low response rates, which limit therapeutic benefits to only a subset of individuals. A deeper understanding of the tumor microenvironment (TME) and the interactions between tumor and immune cells is crucial for overcoming resistance. In this context, the reprogramming of erythroid progenitor cells (EPCs) within the TME has emerged as an important mechanism of immunotherapy resistance. EPCs, a key population in erythroid differentiation, undergo epigenetic reprogramming that underlies various physiological and pathological states. Through epigenetic modifications, EPCs may interact with immune cells and thereby promote tumor immune evasion. This review summarizes EPC reprogramming in the TME from an epigenetic perspective and explores their crosstalk with tumor and immune cells. It also evaluates the therapeutic potential of epigenetic drugs targeting EPCs and discusses future research directions focused on reversing pathological epigenetic reprogramming in EPCs to enhance immunotherapy efficacy. These advances hold significant potential for optimizing clinical cancer care paradigms and improving patient prognosis.