Immune Escape Mechanisms and their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

Immunotherapy has been recently approved for the treatment of relapsed and metastatic head and neck squamous cell carcinoma (HNSCC). However, the response of patients is limited and the overall survival remains short with a low rate of long-term survivors. There exists growing evidence that immune escape mechanisms play an important role for the low efficacy of immunotherapies in this disease. These are caused by diverse complex processes characterized by (i) changes in the expression of immune modulatory factors in tumour cells, (ii) alterations in the frequency and composition of immune cell subpopulations in the tumour microenvironment and peripheral blood leading to reduced innate and adaptive immune responses, (iii) impaired homing of immune cells to the tumour site as well as (iv) the presence of immune suppressive soluble and physical factors in the tumour microenvironment. We here summarize the major immune escape strategies of HNSCC lesions, the role of the tumor microenvironment in this process, the clinical relevance of HNSCC-induced immune tolerance, currently employed immunotherapeutic approaches and possibilities to overcome resistance to immunotherapy thereby improving the HNSCC patients’ survival.