Abstract 1546: Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma

Abstract

Abstract Introduction: Evidence has accumulated indicating that cancer-associated fibroblasts (CAFs) play an important role in angiogenesis, invasion, and metastasis. Simultaneously, CAFs might actively participate in inducing immunosuppressive ability and promoting evasion from immunosurveillance. In the present study, we investigated whether CAFs within the tumor microenvironment contribute as one of key components of tumor immune evasion in head and neck squamous cell carcinoma (HNSCC). Materials and methods: CAFs and normal fibroblasts (NFs) were prepared from surgical tissue of HNSCC patients. Flow cytometric analysis was performed for the expression of A-smooth muscle actin (A-SMA) and co-stimulatory molecules. Inhibition of T-cell proliferation, T-cell apoptosis and induction of regulatory T cells (Treg) were also examined using flow cytometry. The mRNA expression of various cytokines was investigated by real-time qRT-PCR. Results: Generated CAFs and NFs were negative for CD11b, CD34, and CD45, and were positive for CD90 and FAP. The A-SMA expression of CAFs was higher than that of NFs. CAFs efficiently suppressed T cell proliferation as compared with NFs. Of note, this suppressive activity was found under co-cultivation with not only CAFs, but also supernatant from CAFs. CAFs, but not NFs expressed co-regulatory molecules, B7H1 and B7DC and CAFs showed increased expression levels of cytokine genes including IL-6, IL-8, TNF-A, TGF-β, and VEGF. Moreover, PBMCs co-cultured with supernatant from CAFs preferentially induced T-cell apoptosis and Treg as compared with those from NFs. Conclusion: Our findings suggest that, in the tumor microenvironment, CAFs might play a pivotal role in establishing an immunosuppressive network along with tumor cells, and subsequent facilitation to activate the immunosuppressive pathway. Citation Format: Hideyuki Takahashi, Koichi Sakakura, Kazuaki Chikamatsu. Immunosuppressive activity of cancer-associated fibroblasts in head and neck squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1546. doi:10.1158/1538-7445.AM2015-1546