The impact of m6A modified cargo conveyed by exosomes on the tumor microenvironment

The dynamic evolution of tumor microenvironment (TME) is the core of cancer progression. N6-methyladenosine (m6A) modification and exosome transport are key layers of post-transcriptional gene regulation and intercellular communication, respectively. However, the intersection of these two systems, namely the transportation of m6A modified bioactive cargoes through exosomes and reshaping of TME, still lacks systematic sorting. This review aims to fill this gap. Through systematic searches of PubMed, Scopus, and Web of Science, we identified 21 original preclinical studies focused on this area over the past five years. By analyzing these literature, a conceptual framework for the "m6A-exosome axis" was established for the first time, and how it mediates TME and its effects were elucidated. We found that bioactive molecules modified with m6A can be transported to TME through exosomes. During this process, these molecules can reshape existing stromal cells and immune cells, activate tumor associated cytokines, and regulate the malignant phenotype of tumor cells. This TME remodeling further affects pathological processes such as tumor angiogenesis, epithelial mesenchymal transition (EMT), immune escape, metastasis, and drug resistance. These findings indicate that the key components of this axis not only serve as potential biomarker candidates, but also represent a promising preclinical therapeutic target. Targeting this axis provides an innovative combination strategy framework for overcoming tumor growth and metastasis.