title: CD8 down-regulation on cytotoxic T lymphocytes of patients with endometrioid endometrial carcinomas.
abstract: Carcinogenesis is a multistep process in which cancer cells and tumor stroma cells play important roles. T lymphocytes are immune constituents of tumor stroma and play a crucial function in anti-tumor response. By immunohistochemistry and flow cytometry, we studied T cytotoxic (CTLs) and T helper lymphocyte distribution and percentage in the tumor microenvironment and peripheral blood from 35 patients with endometrioid endometrial carcinomas (EEC). We also studied 23 healthy donors' blood samples as a control group. Tumor and non-tumoral endometrium samples were obtained. Immunohistochemistry revealed a high number of CTLs and T helper lymphocytes in the tumor stroma of myoinvasive EECs. T lymphocytes were mostly located in the invasive front. By flow cytometry, the percentages of CTLs and T helper lymphocytes were significantly higher in the tumor compared with the non-neoplastic endometrium (P = .0492 and P = .002). The mean fluorescence intensity of CD8 staining was lower in the tumor compared to the non-neoplastic endometrium (P = .001). There was also reduction of the mean fluorescence intensity of CD8 staining on peripheral blood from patients with grade 3 EECs compare to the peripheral blood from healthy donors (P = .0093). No alterations in the expression of granzymes A and B were found in the CTLs from the EEC cases. Finally, in a proteome profiler cytokine array we found that the growth differentiation factor 15 (GDF15) increased in blood in parallel to the tumor grade. EECs are capable of down-regulating CD8 expression of CTLs. Most likely, this effect is mediated by a soluble molecule present in plasma and is not a result of anergy or exhaustion state.
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Pascual-García
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bértolo
authors.affiliation: Department of Immunology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau), 08041 Barcelona, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Nieto
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Serrat
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
authors.forename: Íñigo
authors.initials: Í
authors.lastname: Espinosa
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain.
authors.forename: Emanuela
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Gynaecology and Obstetrics, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Muñoz
authors.affiliation: Department of Gynaecology and Obstetrics, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Rovira
authors.affiliation: Department of Immunology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau), 08041 Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Vidal
authors.affiliation: Department of Pathology, Hospital de la Santa Creu i Sant Pau. Institute of Biomedical Research (IIB Sant Pau). Autonomous University of Barcelona, 08041 Barcelona, Spain. Electronic address: jprat@santpau.cat.
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D016827:CD8 Antigens / Q000032:analysis*; D018269:Carcinoma, Endometrioid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D016827:CD8 Antigens; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: CD8; Endometrial carcinoma; Flow cytometry; GDF15; T lymphocytes