CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2006-09

AUTHORS

Koji Kono, Hiromichi Kawaida, Akihiro Takahashi, Hidemitsu Sugai, Kosaku Mimura, Naoto Miyagawa, Hideo Omata, Hideki Fujii

ABSTRACT

PURPOSE: Regulatory T cells (T regs) can inhibit immune responses mediated by T cells. It has been shown that there is an increased proportion of T regs in several different human malignancies, although the actual mechanism remains unclear. In the present study, we evaluated the prevalence of CD4(+)CD25high T regs in PBMCs from patients with gastric and esophageal cancers in relation to the clinical outcome. METHODS: PBMCs in 72 patients with gastric cancer and 42 patients with esophageal cancer were evaluated for the proportion of CD4(+)CD25high T cells, as a percentage of the total CD4(+) cells, by flow cytometric analysis with triple-color staining. Actuarial overall survival rates of the patients were analyzed by the Kaplan-Meier method. RESULTS: The percentages of CD4(+)CD25high T cells for cases of gastric cancer (4.9+/-1.2%) and esophageal cancer (5.2+/-2.1%) were significantly higher than those for healthy donors (1.9+/-1.1%, P<0.01). There were significant differences in the prevalence of CD4(+)CD25high T cells between the early and advanced disease stages, both in gastric cancer (stage I vs. III, P<0.05; stage I vs. IV, P<0.05) and esophageal cancer (stage I vs. IV, P<0.05). The patients with a high proportion of CD4(+)CD25high T cells showed poorer survival rates in comparison to those with a low proportion, in both gastric and esophageal cancers. After patients received curative resections of gastric cancers (n=57), the increased proportions of CD4(+)CD25high T cells were significantly reduced, and the levels were almost equal to those in normal healthy donors. In addition, studies of gastric cancer patients with postoperative recurrent tumors (n=6) revealed that the prevalence of CD4(+)CD25high T cells individually increased compared to 2 months after the operations. CD4(+)CD25high T cells expressed FOXP3 mRNA and had abundant CD45RO and intracellular CTLA-4 molecules. CONCLUSIONS: These results strongly suggest that tumor-related factors induce and expand CD4(+)CD25high T regs. More... »

PAGES

1064-1071

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00262-005-0092-8

DOI

http://dx.doi.org/10.1007/s00262-005-0092-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042262663

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16328385


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54 schema:description PURPOSE: Regulatory T cells (T regs) can inhibit immune responses mediated by T cells. It has been shown that there is an increased proportion of T regs in several different human malignancies, although the actual mechanism remains unclear. In the present study, we evaluated the prevalence of CD4(+)CD25high T regs in PBMCs from patients with gastric and esophageal cancers in relation to the clinical outcome. METHODS: PBMCs in 72 patients with gastric cancer and 42 patients with esophageal cancer were evaluated for the proportion of CD4(+)CD25high T cells, as a percentage of the total CD4(+) cells, by flow cytometric analysis with triple-color staining. Actuarial overall survival rates of the patients were analyzed by the Kaplan-Meier method. RESULTS: The percentages of CD4(+)CD25high T cells for cases of gastric cancer (4.9+/-1.2%) and esophageal cancer (5.2+/-2.1%) were significantly higher than those for healthy donors (1.9+/-1.1%, P<0.01). There were significant differences in the prevalence of CD4(+)CD25high T cells between the early and advanced disease stages, both in gastric cancer (stage I vs. III, P<0.05; stage I vs. IV, P<0.05) and esophageal cancer (stage I vs. IV, P<0.05). The patients with a high proportion of CD4(+)CD25high T cells showed poorer survival rates in comparison to those with a low proportion, in both gastric and esophageal cancers. After patients received curative resections of gastric cancers (n=57), the increased proportions of CD4(+)CD25high T cells were significantly reduced, and the levels were almost equal to those in normal healthy donors. In addition, studies of gastric cancer patients with postoperative recurrent tumors (n=6) revealed that the prevalence of CD4(+)CD25high T cells individually increased compared to 2 months after the operations. CD4(+)CD25high T cells expressed FOXP3 mRNA and had abundant CD45RO and intracellular CTLA-4 molecules. CONCLUSIONS: These results strongly suggest that tumor-related factors induce and expand CD4(+)CD25high T regs.
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