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The majority of patients receiving such immunotherapy do not demonstrate durable tumor remission.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Original articles covering tumor heterogeneity, immunoediting, immune escape, and local tumor immunosuppression were reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010based immunotherapy. Even in the setting of optimal immunotherapy, the immunosuppressive tumor microenvironment may arrogate effector immune responses through a number of distinct mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Highly effective immunotherapy will likely require multimodality approaches targeting independent mechanisms of immune activation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.26158","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T10:29:58Z","timestamp":1586514598000},"page":"2722-2733","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mechanisms of resistance to T cell\u2010based immunotherapy in head and neck cancer"],"prefix":"10.1002","volume":"42","author":[{"given":"Maxwell Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Translational Tumor Immunology Program National Institute on Deafness and Other Commination 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