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.

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.Methods: Case-control exploratory study of TCS treated with chemotherapy (³3 BEP cycles, disease-free ³3 months) compared with age matched healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. CDKN2A /p16 INK4a expression in T cells was measured using qPCR. The percentage of lymphocyte subpopulations and the CDKN2A/ p16 INK4a 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 /p16 INK4a 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 /p16 INK4a and a lymphocyte phenotype that has been associated with immunosenescence. Further studies are warranted to define the clinical implications of these alterations in TCS.

e16037 Background: Cytotoxic (Ctx) chemotherapy can cure patients with advanced testicular cancer. Notwithstanding, Ctx agents could promote molecular aging and induce cellular senescence in vivo. This phenomenon has been studied in breast cancer patients exposed to adjuvant chemotherapy, however, the potential induction of premature immunosenescence in testicular cancer survivors (TCS) exposed to chemotherapy remains unknown. Methods: Case-control study. Cases were 18-55 yo TCS, treated with chemotherapy (≥3 BEP cycles), disease-free for ≥3 m. Controls were healthy subjects matched by sex and age ± 1 y. Selected subpopulations of isolated peripheral blood mononuclear cells (PBMC) depicted in Table, were analyzed flow cytometry. Statistics: Adjusted counts or relative percentage for each population were compared using student-t test or Mann-Whitney U test as appropriate. Results: We included 15 TCS and 15 controls. Mean age was 32.6 yo (24-54 y). Mean time since last chemotherapy was 53.13 months (3-192 m). All 15 patients were treated with at least 3 BEP cycles ± TIP/VIP cycles. There were no differences in total leucocyte (5128 ± 1917 vs 5850 ± 2141, p=0.36), and lymphocyte (1539 ± 592 vs 1889 ± 825, p=0.4) counts among cases and controls. Cases have a diminished percentage of CD3+ (63 ± 10 vs 71 ± 11, p=0.05) and CD4+ cells (36±8 vs 43 ± 9, p=0.03). There were no differences in pct of CD8+ or CD19+. However, there was an increase in late differentiated CD8+/CD57+ cells (31 ± 14% vs 20 ± 11%, p=0.02); and a decrease in CD4+/CD28+ cells (90 ± 9% vs 97 ± 4%, p=0.02) in cases. We observed paradoxical changes in B cell subpopulations with an increment in naïve (79 ±10 vs 67% ± 14% p=0.02) and a decrease in memory (18 ± 9 vs 31 ± 13%, p=0.01) B cells. Conclusions: TCS after chemo develop changes compatible with immunesenescence in T cell (CD3+) compartment, and an increment in naïve B cells. [Table: see text]

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.

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