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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2015-11, Vol.64 (11), p.1407-1417
• Main Authors: Takahashi, Hideyuki, Sakakura, Koichi, Kawabata-Iwakawa, Reika, Rokudai, Susumu, Toyoda, Minoru, Nishiyama, Masahiko, Chikamatsu, Kazuaki
• Format: Article
• Language: English
• Subjects: Angiogenesis; Apoptosis; Cancer; Cancer Research; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Cells; Cytokines - genetics; Fibroblasts - physiology; Head and Neck Neoplasms - immunology; Head and Neck Neoplasms - pathology; Humans; Immunology; Insulin-like growth factors; Lymphocyte Activation; Lymphocytes; Medical prognosis; Medicine; Medicine & Public Health; Metastasis; Oligonucleotide Array Sequence Analysis; Oncology; Original; Original Article; Otolaryngology; Penicillin; Radiation therapy; Squamous Cell Carcinoma of Head and Neck; Surgery; T-Lymphocytes, Regulatory - immunology; Tumor Escape; Tumors; Vascular endothelial growth factor
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-015-1742-0

Cancer-associated fibroblasts (CAFs) have been shown to play an important role in angiogenesis, invasion, and metastasis. In the present study, we determined whether CAFs within the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) contributed to promoting immunosuppression and evasion from immune surveillance. Six pairs of CAFs and normal fibroblasts (NFs) were established from the resected tumor tissues of patients with HNSCC. The effects of CAFs and NFs on the functions of T cells were comparatively analyzed. CAFs expressed the co-regulatory molecules, B7H1 and B7DC, whereas NFs did not. The expression levels of cytokine genes, including those for IL6 , CXCL8 , TNF , TGFB1 , and VEGFA , were higher in CAFs. T cell proliferation was suppressed more by CAFs or their supernatants than by NFs. Moreover, PBMCs co-cultured with the supernatants of CAFs preferentially induced T cell apoptosis and regulatory T cells over those co-cultured with the supernatants of NFs. A microarray analysis revealed that the level of genes related to the leukocyte extravasation and paxillin signaling pathways was higher in CAFs than in NFs. These results demonstrated that CAFs collaborated with tumor cells in the TME to establish an immunosuppressive network that facilitated tumor evasion from immunological destruction.