Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells. Issue 1 (17th October 2019)

• Record Type: Journal Article
• Authors: Hladíková, Kamila; Koucký, Vladimír; Bouček, Jan; Laco, Jan; Grega, Marek; Hodek, Miroslav; Zábrodský, Michal; Vošmik, Milan; Rozkošová, Kateřina; Vošmiková, Hana; Čelakovský, Petr; Chrobok, Viktor; Ryška, Aleš; Špíšek, Radek; Fialová, Anna
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-10-17
• Subjects: HNSCC -- Tumor-infiltrating B lymphocytes -- HPV; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0726-6
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : Background: Standard treatment of oropharyngeal squamous cell carcinoma (OPSCC) is associated with high morbidity, whereas immunotherapeutic approaches using PD-1:PD-L1 checkpoint blockade only show moderate response rates in OPSCC patients. Therefore, a better stratification of patients and the development of novel therapeutic protocols are crucially needed. The importance of tumor-infiltrating B cells (TIL-Bs) in shaping antitumor immunity remains unclear; therefore, we analyzed frequency, phenotype, prognostic value and possible roles of TIL-Bs in OPSCC. Methods: We utilized transcriptomic analysis of immune response-related genes in 18 OPSCC samples with respect to human papillomavirus (HPV) status. The density and localization of CD20 +, CD8 + and DC-LAMP + cells were subsequently analyzed in 72 tissue sections of primary OPSCC samples in relation to patients' prognosis. The immunohistochemical approach was supplemented by flow cytometry-based analysis of phenotype and functionality of TIL-Bs in freshly resected primary OPSCC tissues. Results: We observed significantly higher expression of B cell-related genes and higher densities of CD20 + B cells in HPV-associated OPSCC samples. Interestingly, CD20 + TIL-Bs and CD8 + T cells formed non-organized aggregates with interacting cells within the tumor tissue. The densities of both intraepithelial CD20 + B cells and B cell/CD8 + T cell interactions showed prognostic significance, which surpassed HPV positivity and CD8 + TIL density in stratification of OPSCC patients. High density of TIL-Bs was associated with an activated B cell phenotype, high CXCL9 production and high levels of tumor-infiltrating CD8 + T cells. Importantly, the abundance of direct B cell/CD8 + T cell interactions positively correlated with the frequency of HPV16-specific CD8 + T cells, whereas the absence of B cells in tumor-derived cell cultures markedly reduced CD8 + T cell survival. Conclusions: Our results indicate that high abundance of TIL-Bs and high density of direct B cell/CD8 + T cell interactions can predict patients with excellent prognosis, who would benefit from less invasive treatment. We propose that in extensively infiltrated tumors, TIL-Bs might recruit CD8 + T cells via CXCL9 and due to a highly activated phenotype contribute by secondary costimulation to the maintenance of CD8 + T cells in the tumor microenvironment.