PD-1 and PD-L1 Up-regulation Promotes T-cell Apoptosis in Gastric Adenocarcinoma.

Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying

Chiu, Ying-Ming; Tsai, Chung-Lin; Kao, Jung-Ta; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Cheng, Ken-Sheng; Wu, Yi-Ying.

Afiliación

Chiu YM; Division of Allergy, Immunology & Rheumatology, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.
Tsai CL; Department of Nursing, College of Medicine & Nursing, Hungkuang University, Taichung, Taiwan, R.O.C.
Kao JT; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
Hsieh CT; Division of Cardiovascular Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
Shieh DC; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
Lee YJ; Department of Internal Medicine, School of Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan, R.O.C.
Tsay GJ; Department of Pediatrics, Lotung Poh-Ai Hospital, I-Lan, Taiwan, R.O.C.
Cheng KS; Department of Nursing, College of Medicine & Nursing, Hungkuang University, Taichung, Taiwan, R.O.C.
Wu YY; Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

Anticancer Res ; 38(4): 2069-2078, 2018 04.

Article en En | MEDLINE | ID: mdl-29599324

RESUMEN

BACKGROUND/AIM: The programmed death 1 (PD-1) receptor and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of tumor infiltrating T lymphocytes in gastric adenocarcinoma patients are not well-defined. MATERIALS AND METHODS: We characterized the expression of PD-1 and PD-L1 in peripheral blood and tumor infiltrating cells and analyzed the association between PD-1/PD-L1 expression and disease progression in a cohort of 60 patients with Helicobacter pylori infection, including 18 with gastric adenocarcinoma, 23 with gastritis, and 19 asymptomatic controls. RESULTS: Relative to controls, the expression of PD-1 on peripheral blood and tumor infiltrating T cells increased with disease progression. In vitro, T cells induced PD-L1 expression on primary gastric adenocarcinoma epithelial cells in an IFN-Î³-dependent manner, which in turn promoted T cells apoptosis. Blocking of PD-L1 reversed this effect. CONCLUSION: This study provides evidence for a new therapeutic target in gastric adenocarcinoma patients.

Asunto(s)

Adenocarcinoma/inmunología; Apoptosis/genética; Antígeno B7-H1/genética; Linfocitos Infiltrantes de Tumor/fisiología; Receptor de Muerte Celular Programada 1/genética; Neoplasias Gástricas/inmunología; Linfocitos T/fisiología; Adenocarcinoma/genética; Adenocarcinoma/patología; Apoptosis/inmunología; Antígeno B7-H1/metabolismo; Estudios de Casos y Controles; Células Cultivadas; Progresión de la Enfermedad; Células Epiteliales/patología; Células Epiteliales/fisiología; Regulación Neoplásica de la Expresión Génica; Humanos; Linfocitos Infiltrantes de Tumor/patología; Receptor de Muerte Celular Programada 1/metabolismo; Neoplasias Gástricas/genética; Neoplasias Gástricas/patología; Linfocitos T/patología; Regulación hacia Arriba/genética

Palabras clave

Gastric adenocarcinoma; Helicobacter pylori; PD-1; PD-L1; apoptosis

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Linfocitos T / Adenocarcinoma / Linfocitos Infiltrantes de Tumor / Apoptosis / Antígeno B7-H1 / Receptor de Muerte Celular Programada 1 Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Anticancer Res Año: 2018 Tipo del documento: Article Pais de publicación: Grecia

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