Crosstalk between tumor cells and tumor-associated macrophages mediated by extracellular vesicles: Research advances in remodeling the tumor microenvironment in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and ranks third in incidence among all cancer types. Among the treatment strategies for CRC, immunotherapy—particularly approaches targeting modulation of the tumor microenvironment (TME) to prevent immune escape—represents a key component. The interaction and influence between CRC cells and tumor-associated macrophages (TAMs) within the TME have been shown to be closely associated with immune escape and malignant progression in CRC. Among them, extracellular vesicles (EVs) derived from CRC cells (CRC-EVs) can be taken up by TAMs in the TME and regulate their polarization as well as the production of related bioactive substances. Conversely, EVs secreted by TAMs (TAMs-EVs) can be internalized by CRC cells, thereby promoting the malignant biological behaviors, including proliferation, metastasis, and resistance to radiotherapy and chemotherapy. In this review, we focus on the crosstalk between CRC cells and TAMs within the TME, summarizing and integrating current evidence on how CRC-EVs and TAMs-EVs contribute to TME remodeling and thereby influence CRC malignancy, while systematically outlining the cellular signaling pathways involved in this bidirectional communication.