How Risk Factors Affect Head and Neck Squamous Cell Carcinoma (HNSCC) Tumor Immune Microenvironment (TIME): Their Influence on Immune Escape Mechanisms and Immunotherapy Strategy

Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle, such as cigarette smoking, or by viruses, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV). HNSCC remains a clinical challenge, notwithstanding the improvements observed in the past years, involving surgery, radiotherapy, and chemotherapy. Recurrent/metastatic (R/M) disease represents an unmet clinical need. Immunotherapy has improved the prognosis of a small proportion of these patients, but most still do not benefit. In the last decade, several preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME), identifying important differences between smoking-associated and virus-associated HNSCCs. This review aims to present how different etiologies affect the HNSCC TIME, affecting immune escape mechanisms and sensitivity to immunotherapy.

Automated summary

Most head and neck squamous cell carcinomas (HNSCCs) are caused by lifestyle factors such as smoking or virus infections including HPV and EBV. Despite improvements in surgical, radiation, and chemotherapy treatments, recurrent/metastatic (R/M) disease remains a challenge in clinical practice. While immunotherapy has shown promise in a small percentage of patients, the majority still do not benefit. Recent preclinical and clinical studies have explored the HNSCC tumor immune microenvironment (TIME) and identified important differences between smoking-associated and virus-associated HNSCCs, which impact immune escape mechanisms and response to immunotherapy.