CCL17 and CCL22 chemokines within tumor microenvironment are related to infiltration of regulatory T cells in esophageal squamous cell carcinoma.
It has been reported that an increased population of regulatory T cells (T-regs) is one of the reasons for impaired anti-tumor immunity. We investigated the frequency of Foxp3(+) T-regs in tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) of patients with esophageal squamous cell carcinoma (ESCC). Furthermore, in order to elucidate the mechanisms behind T-regs accumulation within tumors, we evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3(+) T-regs. CD4(+)CD25(+)Foxp3(+) T-regs as a percentage of CD4(+) cells were counted by flow cytometry. The frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells in tumors was also evaluated by flow cytometry. Moreover, an in vitro migration assay using T-regs derived from ESCC was performed in the presence of CCL17 or CCL22. The frequency of Foxp3(+) T-regs in TILs was significantly higher than that in the normal esophageal mucosa (24.6 +/- 10.0 vs 7.1 +/- 5.9%, P < 0.01). The frequency of Foxp3(+) T-regs in PBLs of ESCC patients was significantly higher than that in normal healthy donors (7.0 +/- 4.2 vs 2.5 +/- 1.0%, P < 0.01). Furthermore, the frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells within tumors was significantly higher than that of normal esophageal mucosa, and there was a significant correlation between the frequency of CCL17(+) or CCL22(+) cells and Foxp3(+) T-regs in TILs. In addition, the in vitro migration assay indicated that T-regs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3(+) T-regs in ESCC.
Maruyama
T
T
First Department of Surgery, University of Yamanashi, Chuo City, Yamanashi, Japan.
Kono
K
K
Izawa
S
S
Mizukami
Yoshiki
Y
Kawaguchi
Y
Y
Mimura
K
K
Watanabe
M
M
Fujii
H
H
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000556:secondary*; D054414:Chemokine CCL17 / Q000378:metabolism*; D054422:Chemokine CCL22 / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018950:Lipopolysaccharide Receptors; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D054414:Chemokine CCL17; D054422:Chemokine CCL22; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018950:Lipopolysaccharide Receptors