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

Autor: María T. Bourlon, Diego F. Hernández-Ramírez, Guadalupe Lima, Luis Orozco, Y Atisha-Fregoso, Luis Llorente, Hugo E Velázquez, Irene Medina-Rangel, Juan Hinojosa, Ricardo Rios-Corzo, Francisco J. Valentin-Cortez
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Male
Cancer Research
Aging
Lymphocyte
Testicular cancer survivors
CD8-Positive T-Lymphocytes
0302 clinical medicine
Cancer Survivors
Medicine
biology
medicine.diagnostic_test
Immunosenescence
Middle Aged
Neoplasms
Germ Cell and Embryonal
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.anatomical_structure
Oncology
Premature aging
030220 oncology & carcinogenesis
Female
Research Article
Adult
Germ cell tumors
Peripheral blood mononuclear cell
lcsh:RC254-282
CD19
Flow cytometry
Andrology
03 medical and health sciences
Molecular aging
p16INK4a
Testicular Neoplasms
Testicular cancer
Genetics
Humans
neoplasms
Cyclin-Dependent Kinase Inhibitor p16
business.industry
fungi
medicine.disease
030104 developmental biology
biology.protein
Leukocytes
Mononuclear
business
CD8
Zdroj: BMC Cancer
BMC Cancer, Vol 20, Iss 1, Pp 1-7 (2020)
ISSN: 1471-2407
Popis: Background Cytotoxic 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. Methods Case-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. Results We 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). Conclusion In 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.
Databáze: OpenAIRE
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