ABSTRACT: Immune checkpoint blockade (ICB) promotes anti-tumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination _CTLA-4 and _PD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathological analyses demonstrating a relationship between CAF density and a CD8+ T cell-excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of _SMA-expressing CAFs and impaired tumor progression in vivo. Addition of wild-type, but not Endo180-deficient, CAFs in co-implantation studies restricted CD8+ T cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T cell infiltration and enhanced sensitivity to ICB compared to tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors was associated with a poor response to _PD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy.