Mechanisms of resistance to T cell-based immunotherapy in head and neck cancer

Background Most current approved or investigational immunotherapeutic approaches for head and neck squamous cell carcinoma are aimed at activating T cells. The majority of patients receiving such immunotherapy do not demonstrate durable tumor remission. Methods Original articles covering tumor heterogeneity, immunoediting, immune escape, and local tumor immunosuppression were reviewed. Results In the face of immune pressure, subclones susceptible to T cell killing are eliminated, leaving behind resistant tumor clones in a process known as immunoediting. Such subclones of tumor cells that are resistant to T cell killing may remain sensitive to natural killer (NK) cell detection and elimination, suggesting that patients harboring such tumors may benefit from combination of T and NK cell-based immunotherapy. Even in the setting of optimal immunotherapy, the immunosuppressive tumor microenvironment may arrogate effector immune responses through a number of distinct mechanisms. Conclusions Highly effective immunotherapy will likely require multimodality approaches targeting independent mechanisms of immune activation.