Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy

BMC Cancer

Juan Hinojosa¹  Hugo E. Velazquez¹  Luis Orozco¹  Maria T. Bourlon²  Yemil Atisha-Fregoso³  Luis Llorente⁴  Francisco J. Valentin-Cortez⁴  Ricardo Rios-Corzo⁴  Irene Medina-Rangel⁴  Guadalupe Lima⁴  Diego F. Hernandez-Ramirez⁴ 

[1] Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Escuela de Medicina, Universidad Panamericana, Mexico City, Mexico;Department of Hematology and Oncology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, NL, Mexico;Institute of Molecular Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, USA;Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico;

关键词: Testicular cancer survivors;    Germ cell tumors;    Immunosenescence;    Premature aging;    p16INK4a;    Testicular cancer;    Molecular aging;   

DOI  :  10.1186/s12885-020-07383-2

来源: Springer

【 摘 要 】

BackgroundCytotoxic chemotherapy can cure advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy.MethodsCase-control exploratory study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A/p16INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/p16INK4a expression in TCS were compared with the control group using the Wilcoxon signed-rank test.ResultsWe included 16 cases and 16 controls. The median age was 27 years (minimum 24, maximum 54) and the median time on surveillance was 26.5 months (minimum 3, maximum192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had less naïve CD4+ and increased memory CD4+ cells. Within the CD8+ T lymphocytes, TCS exhibited a decrease in the percentage of naïve cells and an increase in CD8 + CD45RA + CD57+ cells. TCS also exhibited decreased memory CD19+ B cells compared to the controls. The relative expression of CDKN2A/p16INK4a in T cells was increased in TCS (mean 1.54; 95% CI of the mean: 1.074–2.005; p = 0.048).ConclusionIn this exploratory study, TCS showed increased expression of CDKN2A/p16INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

【 授权许可】

CC BY