CTL- vs Treg lymphocyte-attracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma

J. Y. Liu, F. Li, L. P. Wang, X. F. Chen, D. Wang, L. Cao, Y. Ping, S. Zhao, B. Li, S. H. Thorne, B. Zhang, P. Kalinski, Y. Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Background: Tumoural infiltration of T lymphocytes is determined by local patterns of specific chemokine expression. In this report, we examined the roles of CCL4 and CCL20 in the accumulation of CD8+ cytotoxic T lymphocytes (CTLs) and regulatory T (Treg) lymphocytes in oesophageal squamous cell carcinoma (ESCC), and determined the correlations between chemokine expressions and ESCC patients' survival. Methods: Reverse transcriptase-PCR and immunohistochemistry (IHC) staining were performed to examine the expressions of interested genes. Flow cytometry was adopted to check the expressions of CCL4- and CCL6-specific receptors, CCR5 and CCR6, on CTLs and Treg cells. In addition, transwell assay was carried on. Results: The CCL4 expression was significantly correlated with the expression of CTL markers (CD8 and Granzyme B), whereas CCL20 was positively correlated with Treg markers (FoxP3 and IL-10). Consistently, CCR5 was found to be mainly expressed on CD8+ T lymphocytes, while CCR6 showed prevalence on Treg lymphocytes and the frequencies of CCR5+ CD8+ CTLs and CCR6+ Treg cells were higher in TIL compared with PBMC. Respectively, CCL4 and CCL20 recruited CD8+ and regulatory T cells in vitro. Importantly, high levels of CCL4 in the lesions of ESCC patients predicted prolonged survival. Furthermore, CCL4high/CCL20low group demonstrated better overall survival, whereas CCL4low/CCL20low and CCL4low/CCL20high groups showed the worst overall survival. Conclusions: Our data showed that CCL4 and CCL20 recruit functionally different T lymphocyte subsets into oesophageal carcinoma, indicating CCL4 and CCL20 are potential predictors of ESCC patients' survival.

Original languageEnglish (US)
Pages (from-to)747-755
Number of pages9
JournalBritish Journal of Cancer
Volume113
Issue number5
DOIs
StatePublished - Sep 1 2015

Keywords

  • CCL20
  • CCL4
  • T lymphocyte
  • chemotaxis
  • oesophageal squamous cell carcinoma
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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