过去十年间，对肿瘤微环境（TME）的广泛研究已经改变了癌症被视为以肿瘤细胞为中心的疾病的看法。肿瘤微环境尤其是所谓的“种子和土壤”理论已经成为癌症发展和治疗抗性的关键因素。TME主要包括肿瘤细胞、成纤维细胞等基质细胞、免疫细胞和其他非细胞组分。在TME中，这些成分之间的密切交流主要决定了肿瘤的命运。基质的关键作用尤其在肿瘤相关成纤维细胞（CAFs），其是TME中最常见的成分，已在肿瘤发生、进展、治疗反应和免疫方面发挥了重要作用。更好地理解 TME 的功能可以为肿瘤治疗提供新方向。在本次评论中，我们总结了对致瘤因素，尤其是 CAF 在癌症进展、耐药性和肿瘤免疫中新兴的认识，并侧重于它们在表观遗传调节中的功能。此外，将进一步讨论表观遗传调节在重塑TME中的重要性，以及表观治疗与免疫治疗之间协同作用的基本生物学原则。©2023年作者.

Extensive studies of the tumor microenvironment (TME) in the last decade have reformed the view of cancer as a tumor cell-centric disease. The tumor microenvironment, especially termed the "seed and soil" theory, has emerged as the key determinant in cancer development and therapeutic resistance. The TME mainly consists of tumor cells, stromal cells such as fibroblasts, immune cells, and other noncellular components. Within the TME, intimate communications among these components largely determine the fate of the tumor. The pivotal roles of the stroma, especially cancer-associated fibroblasts (CAFs), the most common component within the TME, have been revealed in tumorigenesis, tumor progression, therapeutic response, and tumor immunity. A better understanding of the function of the TME sheds light on tumor therapy. In this review, we summarize the emerging understanding of stromal factors, especially CAFs, in cancer progression, drug resistance, and tumor immunity with an emphasis on their functions in epigenetic regulation. Moreover, the importance of epigenetic regulation in reshaping the TME and the basic biological principles underpinning the synergy between epigenetic therapy and immunotherapy will be further discussed.© 2023. The Author(s).