Tumor-infiltrating B cells affect the progression of oropharyngeal squamous cell carcinoma via cell-to-cell interactions with CD8+ T cells

Abstract

BackgroundStandard 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0726-6) contains supplementary material, which is available to authorized users.

Adenosine-producing regulatory B cells in head and neck cancer

“…As more than 50% of B cells can produce adenosine, the same cells are probably also capable of secreting cytokines or to process antigens [29]. In view of this hypothesis, we support the idea that tumor-infiltrating B cells may serve as a positive prognostic marker in cancer patients [30,31]. The correlation between humoral immune responses and different patterns of immune infiltrates in HNSCC patients has been described in detail by Lechner et al [32].…”

Immunological Network in Head and Neck Squamous Cell Carcinoma—A Prognostic Tool Beyond HPV Status

“…In contrast, we observed significantly higher levels of CD45+LIN-HLA-DR+CD14-CD11c+ mDCs in HPV+ oropharyngeal tumors compared to those in HPV-negative HNSCC using flow cytometry (29). However, we did not show any differences between the densities of tumor-infiltrating DC-LAMP+ activated mDCs in HPV+ and HPV-oropharyngeal tumor samples using immunohistochemical staining, and we did not observe any associations between the DC-LAMP+ mDC densities and patient outcomes (43).…”

Complete Pathological Response to Neoadjuvant Pembrolizumab in a Patient With Chemoresistant Upper Urinary Tract Urothelial Carcinoma: A Case Report

“…The existence of tumor-infiltrating B cells (TIL-Bs) had been reported as a factor predicting the efficacy of platinum-based chemotherapy in MIBC (14,15). Moreover, TIL-Bs in the microenvironment of other solid tumors had been reported as a valid prognostic factor given that it provides costimulatory signals important for CD8 + T cell maintenance in tumor tissues (16). This might be one of the reasons for chemotherapy resistance in this case.…”