title: Activation of regulatory T cells instigates functional down-regulation of cytotoxic T lymphocytes in human breast cancer.
abstract: Regulatory T (Treg) cells are a subpopulation of T cells with the ability to control the responses of both CD4+ and CD8+ T cells. A case-control study was conducted in order to determine the functional attributes of Treg cells within the breast cancer milieu. Triple-color flow cytometry was utilized to study the phenotype expression of CD4+CD25+ Treg cells and CD8+ T cells in autologous tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) derived from 33 patients with stage I-III breast cancer. The prevalence of CD4+CD25+ T cells was significantly higher in TILs than in PBLs. The expressions of FOXP3 and GITR in CD4+CD25+ Treg cells were lower in PBLs than in TILs. Functional studies showed that both granzyme B and perforin were barely expressed in peripheral Treg cells but were highly expressed in Treg cells in the tumor microenvironment. On the contrary, down-regulation of both granzyme B and perforin expressed in the CD8+ cytotoxic T lymphocytes was significantly lower in TILs than in PBLs. Further functional assays demonstrated that Th1 cytokines and cytotoxic molecules were synchronously up-regulated in CD8+ cytotoxic T cells. The in vitro kinetic study showed that adequate activation of TILs derived from breast cancer tissue could restore the appropriate antitumor immune response.
authors.affiliation: Department of Surgery, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.
authors.forename: Chao-Hsu
authors.initials: CH
authors.lastname: Li
authors.forename: Wen-Hong
authors.initials: WH
authors.lastname: Kuo
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Chang
authors.forename: Su-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: King-Jen
authors.initials: KJ
authors.lastname: Chang
authors.forename: Bor-Ching
authors.initials: BC
authors.lastname: Sheu
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D053804:Granzymes / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology; D009367:Neoplasm Staging; D054353:Perforin / Q000096:biosynthesis / Q000276:immunology; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009363:Neoplasm Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes