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 p16 INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy. Patients and methods Case-control study of TCS treated with chemotherapy (≥3 BEP cycles, disease-free ≥3 months) compared with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16 INK4a expression in T cells was measured using qPCR. Percentage of lymphocyte subpopulations associated with immunosenescence and p16 INK4a expression in TCS compared to controls using the Wilcoxon signed-rank test.
Results We included 16 cases and 16 controls. The median of age was 27 years (24-54) and median time on surveillance was 26.5 months (3-192). TCS had a lower percentage of total T cells and CD4+ T cells in total lymphocytes. Among the CD4+ T lymphocytes, TCS had a lower naïve CD4+ and an 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 a decreased memory CD19+ B cells compared to the controls. The relative expression of p16 INK4a in T cells was higher in TCS compared to the controls [1.33 (IQR 0.93-2.23): p=0.048).
Conclusion TCS showed an increase in the expression of the aging biomarker p16 INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory cells. This phenomenon might contribute to the development of an immune risk profile, which is associated with an increased rate of infections and a diminished effect of vaccination in the elderly population. Further studies are warranted to define the clinical implications of this alteration in TCS.