Abstract
Head and neck cancer comprises a heterogenous, highly immune infiltrated malignancy, defined by a predominantly immunosuppressive tumor microenvironment (TME). In recent years, PD-1/PD-L1 immune checkpoint inhibitors have become the standard of care treatment, either as monotherapy or in combination with chemotherapy agents, thus revolutionizing the therapeutic landscape of recurrent/metastatic disease. As a result, preclinical research is increasingly focusing on TME composition and pathophysiology, aiming to comprehensively characterize the specific elements and interactions affecting anti-tumor immunity, as well as to unveil novel predictive biomarkers of immunotherapy outcomes. While T lymphocytic populations have been vastly explored regarding their effect on cancer development, B-cells constitute a far less investigated, yet possibly equally important, aspect of cancer immunity. B-cell presence, either as single cells or as part of tertiary lymphoid structures within the TME, has been associated with several anti-tumor defense mechanisms, such as antigen presentation, antibody production and participation in antibody-dependent cellular cytotoxicity, and has demonstrated prognostic significance for multiple types of malignancies. However, immunoregulatory B-cell phenotypes have also been identified both peripherally and within malignant tissue, bearing inhibitory effects on numerous immune response processes. Consequently, B-cells and their subsets demonstrate the potential to become valuable cancer biomarkers and acquire a leading role in future therapeutic strategies.