Immune-Related Mutational Landscape and Gene Signatures: Prognostic Value and Therapeutic Impact for Head and Neck Cancer

SIMPLE SUMMARY: Immunotherapy has emerged as a standard-of-care for most human malignancies, including head and neck cancer, but only a limited number of patients exhibit a durable clinical benefit. An urgent medical need is the establishment of accurate response predictors, which is handicapped by the growing body of molecular, cellular and clinical variables that modify the complex nature of an effective anti-tumor immune response. This review summarizes more recent efforts to elucidate immune-related mutational landscapes and gene expression signatures by integrative analysis of multi-omics data, and highlights their potential therapeutic impact for head and neck cancer. A better knowledge of the underlying principles and relevant interactions could pave the way for rational therapeutic combinations to improve the efficacy of immunotherapy, in particular for those cancer patients at a higher risk for treatment failure. ABSTRACT: Immunotherapy by immune checkpoint inhibition has become a main pillar in the armamentarium to treat head and neck cancer and is based on the premise that the host immune system can be reactivated to successfully eliminate cancer cells. However, the response rate remains low and only a small subset of head and neck cancer patients achieves a durable clinical benefit. The availability of multi-omics data and emerging computational technologies facilitate not only a deeper understanding of the cellular composition in the tumor immune microenvironment but also enables the study of molecular principles in the complex regulation of immune surveillance versus tolerance. These knowledges will pave the way to apply immunotherapy more precisely and effectively. This review aims to provide a holistic view on how the immune landscape dictates the tumor fate and vice versa, and how integrative analysis of multi-omics data contribute to our current knowledge on the accuracy of predictive biomarkers and on a broad range of factors influencing the response to immunotherapy in head and neck cancer.