Skewed distribution of IL-7 receptor-a-expressing effector memory CD8 ⁺ T cells with distinct functional characteristics in oral squamous cell carcinoma

CD8⁺ T cells play important roles in anti-tumor immunity but distribution profile or functional characteristics of effector memory subsets during tumor progression are unclear. We found that, in oral squamous carcinoma patients, circulating CD8⁺ T cell pools skewed toward effector memory subsets with the distribution frequency of CCR7^-CD45RA ^-CD8⁺ T cells and CCR7^- CD45RA ⁺CD8⁺ T cells negatively correlated with each other. A significantly higher frequency of CD127^lo CCR7^-CD45RA ^-CD8⁺ T cells or CCR7^-CD45RA ⁺CD8⁺ T cells among total CD8⁺ T cells was found in peripheral blood or tumor infiltrating lymphocytes, but not in regional lymph nodes. The CD127^hi CCR7^-CD45RA^-CD8 ⁺ T cells or CCR7^-CD45RA⁺CD8⁺ T cells maintained significantly higher IFN-γ, IL-2 productivity and ex vivo proliferative capacity, while the CD127^lo CCR7 ^-CD45RA^-CD8⁺ T cells or CCR7 ^-CD45RA⁺CD8⁺ T cells exhibited higher granzyme B productivity and susceptibility to activation induced cell death. A higher ratio of CCR7^-CD45RA⁺CD8⁺ T cells to CCR7 ^-CD45RA^-CD8⁺ T cells was associated with advanced cancer staging and poor differentiation of tumor cells. Therefore, the CD127^lo CCR7^-CD45RA^-CD8⁺ T cells and CCR7^-CD45RA⁺CD8⁺ T cells are functionally similar CD8⁺ T cell subsets which exhibit late differentiated effector phenotypes and the shift of peripheral CD8⁺ effector memory balance toward CCR7^-CD45RA⁺ CD8⁺ T cells is associated with OSCC progression.