Comparison of T cell response in the tumor milieu of patients with HPV+ and HPV− head and neck cancer

Abstract

Background: The incidence of HPV-associated squamous cell carcinoma of the head and neck region (HNSCC) has increased dramatically in recent years. Despite a similar localization (oropharyngeal squamous cell epithelia) to smoking- and alcohol-associated cancers, HPV-associated carcinomas are considered to represent a distinct entity. Reasons for the different therapeutic responses of the two tumor entities are not yet fully understood. Methods and objective: This review investigates the importance of tumor-infiltrating lymphocytes in HPV+ and HPV− HNSCC by means of articles and publications concerning the tumor micromilieu, effects on prognosis, and patients’ therapeutic responses. Results: HNSCC patients with a positive HPV status and increased frequencies of CD8+ T cells (CD, cluster of differentiation) demonstrated an improved therapeutic response and improved outcomes. Decreased expression of the EGF (epidermal growth factor) receptor correlates with increased TH1 cytokine secretion by CD4+ T cells, which, in their role as T helper cells, can activate macrophages, dendritic cells, and cytotoxic T cells, amongst others. Regulatory T cells (Treg) execute an immune-suppressive effect in the tumor micromilieu through different metabolic and signaling pathways (IL[interleukin]‑4, IL-10, TGF‑β [„transforming growth factor‑β“]). Conclusion: The importance of the adaptive immune response for treatment response and patients’ prognosis has been supported by different investigations. Understanding the immunological processes in the tumor environment plays an important role for the development of new treatment approaches.