Heterogeneity of tumor-associated macrophages in colorectal cancer: Origins, classification, and immunotherapeutic implications

Tumor microenvironment (TME) plays an important role in the occurrence, progression, and therapeutic response of malignant tumor. As the main immune cells in TME, tumor-associated macrophages (TAMs) are considered to be potential key targets for cancer diagnosis and treatment. However, the functional roles and clinical significance of TAMs in colorectal cancer (CRC) remains controversial. These controversies may stem from the dynamic changes in TME and the high heterogeneity of TAMs. In this review, we systematically explore the sources, classification, identification methods and clinical significance of TAM heterogeneity in CRC. We also summarize current therapeutic approaches targeting TAMs and their limitations. In addition, differences in the function of TAMs in different stages and subtypes of CRC were analyzed, highlighting their interactions with other immune cells and signaling pathways. It suggests that developing novel therapeutic strategies based on TAM heterogeneity holds promise for advancing precision monitoring and treatment of CRC, and promote the further development of tumor immunotherapy.