Tumor Microenvironment and Immunotherapy Response in Head and Neck Cancer

Simple Summary Immunotherapy has revolutionized cancer treatment and has been integrated in the treatment algorithm of metastatic head and neck cancer. Despite robust clinical efficacy shown in clinical trials, only a minority of patients derive benefit from immunotherapy. Indeed, an important parameter that affects the effectiveness of immunotherapeutic drugs is the tumor microenvironment (TME), whose cellular elements participate in tumor evolution and metastasis. Through interaction with TME cells, tumor cells have the capacity to generate an immunosuppressive TME that may substantially influence the response to immunotherapy. In this review, we aim to illustrate the complex interplay between TME cells and describe their potential role as therapeutic targets with the goal to overcome treatment resistance. The tumor microenvironment (TME) encompasses cellular and non-cellular components which play an important role in tumor evolution, invasion, and metastasis. A complicated interplay between tumor cells and adjacent TME cells, such as stromal cells, immune cells, inflammatory cells, and cytokines, leads to severe immunosuppression and the proliferation of cancer cells in several solid tumors. An immunosuppressive TME has a significant impact on treatment resistance and may guide response to immunotherapy. In head and neck cancer (HNC), immunotherapeutic drugs have been incorporated in everyday clinical practice. However, despite an exceptional rate of durable responses, only a low percentage of patients respond. In this review, we will focus on the complex interactions occurring in this dynamic system, the TME, which orchestrate key events that lead to tumor progression, immune escape, and resistance. Furthermore, we will summarize current clinical trials that depict the TME as a potential therapeutic target for improved patient selection.