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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.

plos one

Skewed Distribution of IL-7 Receptor-α-Expressing Effector Memory CD8+ T Cells with Distinct Functional Characteristics in Oral Squamous Cell Carcinoma