Author(s): Jang-Jaer Lee 1, Chiou-Yueh Yeh 2, Chiau-Jing Jung 2, Ching-Wen Chen 2, Mao-Kuang Du 2, Hui-Ming Yu 3, Chia-Ju Yang 2, Hui-yi Lin 4, Andy Sun 1, Jenq-Yuh Ko 5, Shih Jung Cheng 1, Yen-Liang Chang 6, Jean-San Chia 2,4,*
CD8+ T cells play important roles in mediating anti-tumor immunity and adoptive transfer-based immunotherapy may achieve regression of tumors . Oral cancer, which is primarily squamous cell carcinoma (OSCC), is the fifth most common cancer world-wide . Compared to conventional treatment for oral or head and neck cancers, adoptive transfer-based immunotherapy is a relatively specific approach directed to tumor cells through the activated effectors such as CD8+ T cells, in an antigen-dependent manner -. In patients with oral or head and neck squamous cell carcinoma, wild-type p53-specific cytotoxic CD8 + T cells play a direct role in the elimination of tumor cells expressing the p53264-272 epitope and in immunoselection of epitope-lost tumor cells carrying mutated-p53 . Interestingly, cytotoxic CD8+ T cells in metastatic lymph nodes, but not in tumor infiltrating lymphocytes, are associated with favorable outcome in patients with OSCC , implicating that CD8+ T cells could mediate systemic protective immune response despite of the immunoselection or immunosuppression occurred locally in OSCC microenvironment -.
Human peripheral CD8+ T cells are heterogeneous populations and could be identified by their surface expression of glycoproteins (e.g. CCR7, CD45RA), or costimulatory molecules (e.g. CD27, CD28) -. Naive CD8+ T cells express high molecular weight isoforms of leukocyte common antigen CD45RA, CD28 and CCR7, a lymph-node-homing chemokine receptor. Human memory CD8+ T cells express the low molecular weight isoform of the common leukocyte antigen CD45RO and can be classified into CCR7+ "central memory" cells and CCR7- "effector memory" cells . However, CD45RA, originally considered to be marker for naive CD8+ T cells, can also found in human memory CD8+ T cells, which have been termed "effector memory RA" (T EMRA ) or "revertant memory" cells because of their re-expression of CD45RA and effector memory-like phenotypes . Interestingly, the T EMRA may resume proliferative responses after receiving the appropriate costimulatory signals . A most recent report indicated that the low frequency of circulating CD8+ CCR7+ T cells is a significant risk factor for tumor recurrence in patients with head and neck cancer , suggesting that skewed distribution of functionally distinct CD8+ T-cell subset may occur during cancer progression.
Circulating CD8+ T cells in oral or head and neck cancer patients have been well-characterized for their susceptibility to apoptosis and the responsible Fas/FasL or TRAIL/TRAILR signaling pathway -. However, the distribution profiles or functional characteristics of the specific CD8 + T-cell subsets in either tumor infiltrating lymphocytes or systemic circulation of cancer patients are still unclear. Moreover, the identification or isolation of specific effector memory subsets exhibiting ex vivo proliferative capacity and resistant to activation induced cell death is important clinically for conducing adoptive-transfer based cancer immunotherapy . IL-7 signaling...