Cancer-Associated Fibroblasts Suppress CD8+ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade

Immune-checkpoint blockade (ICB) promotes antitumor 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 αCTLA4 and αPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with…

• A
  AstraZeneca
• RM
  Royal Marsden NHS Foundation Trust
• NB
  NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
• NI
  National Institute for Health and Care Research
• DO
  Department of Health and Social Care
• BA
  Biotechnology and Biological Sciences Research Council

  Award: BB/M016099/1