Overcoming barriers to effective immunotherapy: MDSCs, TAMs, and Tregs as mediators of the immunosuppressive microenvironment in head and neck cancer

•The majority of head and neck cancers display high effector immune cell infiltration.•Head and neck cancer cells utilize many defined mechanisms to escape immune elimination.•An immunosuppressive immune infiltrate contributes heavily to local immune suppression.•Modulation of immune escape mechanisms may enhance responses to standard and immune therapies.

SummaryA significant subset of head and neck cancers display a T-cell inflamed phenotype, suggesting that patients with these tumors should respond to therapeutic approaches aimed at strengthening anti-tumor immune responses. A major barrier to the development of an effective anti-tumor immune response, at baseline or in response to immunotherapy, is the development of an immunosuppressive tumor microenvironment. Several well described mechanisms of effector immune cell suppression in the head and neck cancer microenvironment are discussed here, along with updates on current trials designed to translate what we have learned from pre-clinical and correlative clinical studies into improved responses in patients with head and neck cancer following immune activating therapies.