Interactions between cancer cells and tumor-associated macrophages in tumor microenvironment.

Tumor microenvironment (TME) refers to the local environment in which various cancer cells grow, encompassing tumor cells, adjacent non-tumor cells, and associated non-cellular elements, all of which collectively promote cancer occurrence and progression. As a principal immune component in the TME, tumor-associated macrophages (TAMs) exert a considerable influence on cancer behaviors via their interactions with cancer cells. The interactive loops between cancer cells and TAMs, including secretory factors derived from both cancer cells and TAMs, are crucial for the proliferation, stemness, drug resistance, invasion, migration, metastasis, and immune escape of various cancers. Cancer cells release paracrine proteins (HMGB1, AREG etc.), cytokines (IL-6, CCL2 etc.), RNAs (miR-21-5p, circPLEKHM1, LINC01812 etc.), and metabolites (lactic acid, succinate etc.) to regulate the polarization phenotype, mediator secretion and function of TAMs. In turn, mediators (TGF-β, IL-10, IL-6 etc.) from TAMs promote cancer progression. This review summarizes recent advancements in the interactive loops between cancer cells and TAMs in TME. Inhibiting the recruitment and M2 polarization of TAMs, reprogramming TAMs from M2 to M1 phenotype, blocking TAMs-mediated immunosuppression and immune escape, and combining with existing immunotherapy can target TAMs to overcome immunotherapy resistance in various cancers. The new breakthroughs lie in identifying effective targets for drug development, improving the drug delivery system to enhance the drug delivery efficiency, and adopting combined therapy. Interventions targeting secretory factors, cell surface receptors, intracellular signaling pathways, and metabolic modulation in the interactive loops between cancer cells and TAMs are expected to suppress cancer progression and improve therapeutic effects.