Perspective Article

Targeting myofibroblastic cancer-associated fibroblasts (myCAFs): a promising strategy for overcoming tumor progression and immunotherapy resistance

¹ Department of Breast Surgery (Surgical Oncology), Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang 310000, China
² Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, Zhejiang 310000, China
³ Cancer Centre, Zhejiang University, Hangzhou, Zhejiang, China Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China

^* Corresponding author: chenzhigang@zju.edu.cn

Received: 31 December 2024
Accepted: 21 February 2025

Abstract

Cancer-associated fibroblasts (CAFs), as the dominant stromal cell population in the tumor microenvironment (TME), exhibit substantial heterogeneity, with subtypes such as myofibroblastic cancer-associated fibroblasts (myCAFs) and inflammatory cancer-associated fibroblasts (iCAFs) playing distinct roles in cancer progression. MyCAFs, defined by elevated ACTA2 expression, are particularly significant in promoting tumor growth, remodeling the stroma, and contributing to an immunosuppressive TME. Despite advances in understanding CAF heterogeneity, the precise role of myCAFs in tumor invasion, metastasis, and resistance to therapies, especially immunotherapy, remains underexplored. This perspective highlights recent insights into myCAF functions within the TME, emphasizing their potential as therapeutic targets. By disrupting myCAF formation or combining myCAF-targeting approaches with immunotherapy, there is a significant promise for improving treatment outcomes and overcoming immunotherapy resistance in cancer.