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 CD127lo 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 CD127hi 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 CD127lo 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 CD127lo 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.