Identification of B Cell Subpopulations with Pro- and Anti-Tumorigenic Properties in an Immunocompetent Mouse Model of Head and Neck Squamous Cell Carcinoma.

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a very heterogeneous cancer entity with an unsatisfactory prognosis. Despite intensive research and the use of new therapeutic options such as immunotherapy, the 5-year survival rate is not higher than 50% for male individuals, meanly affected by HNSCC, and has not been significantly improved over the last 20 years. The immunosuppressive microenvironment, which is characteristic of head and neck tumors (HNCs), contributes significantly to the failure of new therapy concepts. Therefore, the aim of this work was to identify pro- and anti-tumorigenic immune cell populations in the HNSCC tumor environment with a special focus on the B cell subsets, as recent data assign B lymphocytes a significant contribution to tumorigenesis. In addition to an increase in anti-tumorigenic germinal center (GC) B cells, we describe here for the first time the population of marginal zone (MZ) B cells in the tumor microenvironment (TME) of HNSCC with pro-tumorigenic potential. Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed. Additionally, immunoglobulin (Ig) levels post-tumor induction were tracked via enzyme-linked immunosorbent assays (ELISA). Following tumor induction, GCs, as well as increasing numbers of GL7⁺CD95⁺ GC B cells in the spleen and tumor tissues, were detected. In parallel, we observed CD39⁺CD73⁺ B cells in tumors and spleens of tumor-bearing mice. Notably, CD39⁺CD73⁺ expression was primarily detected on MZ B cells and to a lesser extent on follicular (FO) and non-follicular, newly formed (NF) B cells, supposing an immunosuppressive function of MZ B cells in the TME. Parallel to increased MZ B cell numbers in secondary lymphoid organs (SLOs) as well as in the tumor tissue, IgM antibody (Ab) levels rose continuously. In contrast, IgG1, IgG2, and IgG3 levels increased at later time points. Understanding the complex interactions between B cell subsets and the TME could lead to new strategies for enhancing the treatment and prognosis of HNSCC patients. [ABSTRACT FROM AUTHOR]