Skewed distribution of IL-7 receptor-α-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.
Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Jang-Jaer
JJ
Lee
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chiou-Yueh
CY
Yeh
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chiau-Jing
CJ
Jung
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Ching-Wen
CW
Chen
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Mao-Kuang
MK
Du
Genomic Research Center, Academic Sinica, Taipei, Taiwan, ROC.
Hui-Ming
HM
Yu
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Chia-Ju
CJ
Yang
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Hui-Yi
HY
Lin
Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Andy
A
Sun
Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Jenq-Yuh
JY
Ko
Department of Oral Maxillofacial Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
Shih Jung
SJ
Cheng
Fu Jen Catholic University, School of Medicine, and Department of Otolaryngology, Cathay General Hospital, Taipei, Taiwan, ROC.
Yen-Liang
YL
Chang
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC ; Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Jean-San
JS
Chia
D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D009062:Mouth Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D054400:Receptors, CCR7 / Q000378:metabolism; D014407:Tumor Cells, Cultured
C515370:CCR7 protein, human; D007376:Interleukin-2; D053699:Interleukin-7 Receptor alpha Subunit; D054400:Receptors, CCR7; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens