Desbois and Wang summarized the roles of cancer-associated fibroblasts (CAFs) in the TME and their impact on immunotherapy efficacy. Using FAP, SMA, and CD29 markers, four functionally distinct CAF populations were identified in breast and ovarian cancer, including immunosuppressive CAF-S1(FAPhiCD29med/hiSMAhi) and contractile CAF-S4 (FAP-CD29hiSMAhi). In tumors with efficient immune cell infiltration, CAFs have antitumor roles (CD8+ T cell recruitment and cell trafficking) and pro-tumor roles (immunosuppressive cell recruitment and polarization, and Treg activation and retention).
Contributed by Katherine Turner
ABSTRACT: Cancer immunotherapies have rapidly changed the therapeutic landscape for cancer. Nevertheless, most of the patients show innate or acquired resistance to these therapies. Studies conducted in recent years have highlighted an emerging role of cancer-associated fibroblasts (CAFs) in immune regulation that shapes the tumor immune microenvironment (TIME) and influences response to cancer immunotherapies. In this review, we outline recent advances in the understanding of phenotypic and functional heterogeneity of CAFs. We will focus on emerging roles of CAFs in shaping the TIME, especially under a framework of tumor immunity continuum, and discuss current and future CAF-targeting therapeutic strategies in particular in the context of optimizing the success of immunotherapies.
Author Info: (1) Department of Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (2) Department of Oncology Biomarker Development, Genentech, Inc., South San Franci
Author Info: (1) Department of Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA. (2) Department of Oncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
