Abstract B91: Plasmacytoid dendritic cells in HPV+ and HPV- head and neck cancer

Abstract

Abstract Introduction: Plasmacytoid dendritic cells (pDC) are the most important IFN type I producing cells. They play an essential role in viral infections; however, they are studied in context of many pathologic conditions including malignancies. Data show their negative effect on patient prognosis in breast, ovarian, skin and oral cancer, but also a possible antitumoral effect is discussed. In case of head and neck cancer (HNSCC), it is assumed that tumor-infiltrating pDC (TIpDC) are dysfunctional and support immunosuppressive environment. Hence, there are no data on the functional state of pDC in relation to HPV status of tumors, despite the fact that a dominant part of oropharyngeal cancer is viral-driven, having better prognosis. Methods: Phenotype and functional state of pDC in tumor-derived single-cell suspensions, tonsils and PBMC was analyzed by flow cytometry. Plasmacytoid DC were identified as CD45+, Lineage -, CD4+, BDCA2+, CD123+ cells. Expression of stimulatory and regulatory molecules (TLR7, TLR 9, NKp44, TIM3, IDO, Granzyme B) was assessed. Cytokine levels in cell culture supernatants were detected using Luminex (IFNα, IFNγ, IL-10, IL-12, IL-17, IL-3, IL-4, IL-6, TNFα, TNFβ). For stimulatory tests CpG A 2216 and Imiquimod were used. Results: We found higher proportions of circulating pDC in HPV+ patients (p=0.045). However, there was no difference in numbers of TIpDC in HPV+ and HPV- HNSSC. We also observed the same number of TIpDC able to react to TLR 7 and TLR 9 stimulation. Nevertheless, pDC from HPV+ tumors showed a potential to produce significantly higher levels of IFNα upon CpG A stimulation (p=0.013). In relation to this, surprisingly, NKp44 expression, referred as negative regulator of IFNα secretion in tonsils, was higher in HPV+ patients (p=0.049). There was no correlation with other regulatory molecules expressed on pDC nor the number of tumor-infiltrating Tregs. Conclusion: Plasmacytoid DC might play an important role in regulation of tumor microenvironment in patients with HNSCC. Our data show functional differences between pDC infiltrating HPV+ and HPV- cancer, suggesting that these cells contribute to the different biology and prognosis of HPV-induced cancer. Citation Format: Vladimír Koucký, Kamila Hladíková, Jan Bouček, Anna Fialová. Plasmacytoid dendritic cells in HPV+ and HPV- head and neck cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B91.