The Immune Cells in the Development of Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: The cells of the immune system can exert a dual effect on cancer development and growth. On the one hand, the immune system can be activated by tumor antigens and can elicit an antitumor response. On the other, the inflammatory milieu in the tumor microenvironment can trigger immune effector mechanisms that promote tumor growth. In the oral cavity, the balance between protumor and antitumor immunity can influence the progression from premalignancy to carcinoma. In this article, we review the cells and mechanisms that are thought to be the most important immune determinants of oral cancer development and progression. ABSTRACT: A still unresolved issue surrounding tumor formation concerns the role that the immune system plays in preventing the formation and progression of neoplasia, including oral squamous cell carcinoma (OSCC). Antitumor immunity has historically been seen as a critical barrier for cancer cells to develop, grow and spread, and this can be modulated using immunotherapies to achieve antitumor clinical responses. However, it has recently become clear that tumor-associated immunity, particularly the inflammatory microenvironment, has the paradoxical effect of enhancing tumorigenesis and progression. In this review, we discuss the multifaceted function of infiltrating immune cells in suppressing or promoting premalignancy and cancer. In particular, we report on the evidence supporting a role for T lymphocytes, dendritic cells, macrophages, and neutrophils in the development and progression of oral potentially malignant disorders (OPMD) and OSCC. We also draw attention to the clinical relevance of immune cell phenotypes and associated molecules for use as biomarkers and to the translatability of current research findings to improve classification systems and precision medicine in patients with OSCC.