Myeloid-derived suppressor cells in cancer: biology, regulatory networks and theranostic prospects

Despite the remarkable progress in cancer treatment, drug resistance and immune escape still severely limit clinical efficacy, largely due to tumor-induced immunosuppression. The main driver of this suppressive environment is myeloid-derived suppressor cells (MDSCs). Tumor-derived cytokines and chemokines can induce the expansion, activation, and recruitment of MDSCs, enabling them to effectively protect tumor cells from being recognized and cleared by immune cells by establishing an immunosuppressive barrier in peripheral lymphoid organs and the tumor microenvironment (TME). Upon arrival in the TME, MDSCs may alter their gene expression patterns through metabolic reprogramming, undergo skewed differentiation toward tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), and initiate immunosuppression to promote tumor growth. Furthermore, they can shape an environment conducive to tumor development and metastasis through various nonimmune mechanisms. Currently, the overall understanding of the systematic integration of MDSC biological properties into therapeutic strategies remains underdeveloped. Therefore, in this review, we systematically summarize: (i) the classification and identification of MDSCs; (ii) their biological properties in the context of tumors and autoimmune diseases; (iii) tumor-promoting effects; (iv) genetic and signaling pathway regulatory mechanisms; (v) differentiation skewing in the TME; and (vi) cellular interactions with the TME. We also propose the clinical potential of MDSC-based predictive and prognostic biomarkers and outline strategies for targeting MDSCs for oncotherapy.