Naive Treg-like CCR7+ mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma

Jie Yi Shi, Meng Duan, Qi Man Sun, Liuxiao Yang, Zhi Chao Wang, Ospan A. Mynbaev, Yi Feng He, Ling Yan Wang, Jian Zhou, Qi Qun Tang, Ya Cao, Jia Fan, Xiao Ying Wang, Qiang Gao

Research output: Contribution to journalArticle

Abstract

Chemokine receptor-like 1 (CCRL1) has the potential in creating a low level of CCL19 and CCL21 to hinder CCR7+ cell tracking to tumor tissue. Previously, we found a tumor suppressive role of CCRL1 by impairing CCR7-related chemotaxis of tumor cells in human hepatocellular carcinoma (HCC). Here, we reported a contribution of CCR7+ mononuclear cells in the tumor microenvironment to the progression of disease. Immunohistochemistry was used to investigate the distribution and clinical significance of CCR7+ cells in a cohort of 240 HCC patients. Furthermore, the phenotype, composition, and functional status of CCR7+ cells were determined by flow cytometry, immunofluorescence, and in vitro co-culture assays. We found that CCR7+ mononuclear cells were dispersed around tumor tissue and negatively related to tumoral expression of CCRL1 (P <0.001, r = 0.391). High density of CCR7+ mononuclear cells positively correlated with the absence of tumor capsule, vascular invasion, and poor differentiation (P <0.05). Survival analyses revealed that increased number of CCR7+ mononuclear cells was significantly associated with worse survival and increased recurrence. We found that CCR7+ mononuclear cells featured a naive Treg-like phenotype (CD45RA+CD25+FOXP3+) and possessed tumor-promoting potential by producing TGF-β1. Moreover, CCR7+ cells were also composed of several immunocytes, a third of which were CD8+ T cells. CCR7+ Treg-like cells facilitate tumor growth and indicate unfavorable prognosis in HCC patients, but fortunately, their tracking to tumor tissue is under the control of CCRL1.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalTumor Biology
DOIs
Publication statusAccepted/In press - Jan 26 2016
Externally publishedYes

    Fingerprint

Keywords

  • CCR7
  • CCRL1
  • Treg-like
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research

Cite this

Shi, J. Y., Duan, M., Sun, Q. M., Yang, L., Wang, Z. C., Mynbaev, O. A., ... Gao, Q. (Accepted/In press). Naive Treg-like CCR7+ mononuclear cells indicate unfavorable prognosis in hepatocellular carcinoma. Tumor Biology, 1-9. https://doi.org/10.1007/s13277-015-4647-9