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

Abstract

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.

• Authors: Jang-Jaer Lee, Chiou-Yueh Yeh, Chiau-Jing Jung, Ching-Wen Chen, Mao-Kuang Du, Hui-Ming Yu, Chia-Ju Yang, Hui-Yi Lin, Andy Sun, Jenq-Yuh Ko, Shih Jung Cheng, Yen-Liang Chang, Jean-San Chia
• Journal: PloS one (PLoS One) Vol. 9 Issue 1 Pg. e85521 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24465587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR7 protein, human
• Interleukin-2
• Interleukin-7 Receptor alpha Subunit
• Receptors, CCR7
• Interferon-gamma
• Leukocyte Common Antigens

Topics

• Apoptosis
• CD8-Positive T-Lymphocytes (metabolism)
• Carcinoma, Squamous Cell (immunology, metabolism, pathology)
• Case-Control Studies
• Cell Proliferation
• Disease Progression
• Humans
• Immunologic Memory
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Interleukin-7 Receptor alpha Subunit (metabolism)
• Leukocyte Common Antigens (metabolism)
• Mouth Neoplasms (immunology, metabolism, pathology)
• Receptors, CCR7 (metabolism)
• Tumor Cells, Cultured