Correlation between CD41CD251Treg Cells and CCR4 in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a head and neck malignancy with high incidence in Southeast Asia, Africa, western Canada and Alaska. In China, NPC has a high prevalence in Guangdong, Guangxi, Hunan, Jiangxi, Fujian, and Yunnan provinces. For instance, the incidence of NPC in Guangdong province is 30–50 per 100,000 annually[1]. CD4+CD25+ regulatory T cells are defined as a subgroup of regulatory T (Treg) cells associated with autoimmune disorders. Transferring CD4+CD25+ Treg cells into BALB/c athymic nude (nu/nu) mice can spontaneously induce the development of histologically and serologically evident autoimmune diseases[2]. Constantly reconstituting the CD4+CD25+ Treg cell population within a limited period after transfer ofCD4+CD25+ Treg cells might prevent those autoimmune diseases[2]. CD4+CD25+ Treg cells may suppress antigen presenting cells or cytotoxic T lymphocytes through cellular interaction or secretion of cytokines. It has been found that in most malignancies, especially in early-stage malignancies, immunosuppression is restricted to the tumor sites. The ratio of CD4+ to CD8+ is the most common measure of immune function, but it does not correlate well with tumor stages, tumor volume or survival rate of patients. Therefore, estimating the immune strength of patients with cancer using the CD4+/CD8+ ratio does not provide a reliable prognosis[3]. For some human cancers, the antigen recognized by T cells is autologous, indicating that tumor immunity is also autoimmunity[4]. CD4+CD25+ Treg cells recognize antigen in a way similar to that of traditional T cells, but the former are activated more easily by autoantigen owing to their higher affinity to autologous tissue[5]. Therefore, it has been hypothesized that immunosuppression in tumor microenvironments is associated with the activation of CD4+CD25+ Treg cells. Chemokines are a group of small, structurally related cytokines which might induce directional migration of different lymphocyte populations, and play important roles in the immune response to infection and tumor. Chemokines are classified into four main subfamilies based on the arrangements of their N-terminal conserved cysteine residues: CXC (a-chemokine), CC (b-chemokine), C (c-chemokine, just the second and fourth cysteine residue), CX3C (d-chemokine)[6]. CC chemokine receptor 4 (CCR4) is a member of the CC chemokine receptor family. In gastric adenocarcinoma, elevated levels of CCL22 and CCL17 (both ligands of CCR4), and an increased number of CD4+CD25+ Treg cells, can be found[7]. This leads to the hypothesis that tumor cells secrete CCL22 and CCL17 which activate and attract CD4+CD25+ Treg cells through the CCR4 pathway, and hence these ligands stimulate the CD4+CD25+ Treg cells which accumulate in tumor sites and suppress immunity. We analyzed the number of CD4+CD25+ Treg cells and the levels of CCR4 in venous blood and in tumor biopsy specimens taken from patients with primary NPC before treatment and from healthy donors using flow cytometry.