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 language||English (US)|
|Number of pages||9|
|State||Accepted/In press - Jan 26 2016|
- Tumor microenvironment
ASJC Scopus subject areas
- Cancer Research