Lymphocyte infiltrates have been observed in the microenvironment of oral cancer; however, little is known about whether the immune response of the lymphocyte infiltrate affects tumor biology. For a deeper understanding of the role of the infiltratinglymphocytes in oral squamous cell carcinoma (OSCC), we characterized the lymphocyte infiltrate repertoires and defined their features. Immunohistochemistry revealed considerable T and B cell infiltrates and lymphoid follicles with germinal center-like structures within the tumor microenvironment. Flow cytometry demonstrated that populations of antigen-experienced CD41 and CD81 cells were present, as well as an enrichment of regulatory T cells; and T cells expressing programmed death-1 (PD-1) and T cell Ig and mucin protein-3 (Tim-3), indicative of exhaustion, within the tumor microenvironment. Characterization of tumorinfiltrating B cells revealed clear evidence of antigen exposure, in that the cardinal features of an antigen-driven B cell response were present, including somatic mutation, clonal expansion, intraclonal variation and isotype switching. Collectively, our results point to an adaptive immune response occurring within the OSCC microenvironment, which may be sustained by the expression of specific antigens in the tumor.Oral cancer is the sixth most common cancer in the world, most of which is oral squamous cell carcinoma (OSCC), accounting for 3% of all malignancies and increasing by 275,000 new cases per year.1,2 Oral cancer is life-threatening because of its invasion of critical structures responsible for speaking, swallowing, and respiration. 3 The treatment of oral cancer has advanced considerably from surgery to a comprehensive sequential treatment that include surgery in combination with chemoradiotherapy; however, the 5-year survival rate has not significantly improved in recent decades, primarily because of its extreme malignancy, including local metastasis, and high recurrence potential. 3,4 Thus, more substantial efforts have stimulated in developing more effective treatments in order to improve the survival rate. Due to the progress in the field of tumor immunology, immunotherapy emerges as a promising option.
5,6The immune response between host and tumor is extremely complex. The function of immune system is to eliminate alien cells; however within the tumor microenvironment, tumor cells escape the immune surveillance and