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

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

10.21203/rs.2.13836/v2 ◽

2019 ◽

Author(s):

Maria Teresa Bourlon ◽

Hugo E Velazquez ◽

Juan Hinojosa ◽

Luis Orozco ◽

Ricardo Rios-Corzo ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Testicular Cancer ◽

Cancer Survivors ◽

Germ Cell Tumors ◽

Lymphocyte Subpopulations ◽

Lower Percentage ◽

Rank Test ◽

P16 Ink4a ◽

Testicular Cancer Survivors

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

10.21203/rs.2.13836/v3 ◽

2020 ◽

Author(s):

Maria Teresa Bourlon ◽

Hugo E Velazquez ◽

Juan Hinojosa ◽

Luis Orozco ◽

Ricardo Rios-Corzo ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Testicular Cancer ◽

Cancer Survivors ◽

Exploratory Study ◽

Lymphocyte Subpopulations ◽

Lower Percentage ◽

Control Group ◽

P16 Ink4a ◽

Testicular Cancer Survivors

Abstract 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.

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

BMC Cancer ◽

10.1186/s12885-020-07383-2 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Maria T. Bourlon ◽

Hugo E. Velazquez ◽

Juan Hinojosa ◽

Luis Orozco ◽

Ricardo Rios-Corzo ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Testicular Cancer ◽

Cancer Survivors ◽

Exploratory Study ◽

Germ Cell Tumors ◽

Lymphocyte Subpopulations ◽

Lower Percentage ◽

Control Group ◽

Testicular Cancer Survivors

Abstract 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.

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

10.21203/rs.2.13836/v4 ◽

2020 ◽

Author(s):

Maria Teresa Bourlon ◽

Hugo E Velazquez ◽

Juan Hinojosa ◽

Luis Orozco ◽

Ricardo Rios-Corzo ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Testicular Cancer ◽

Cancer Survivors ◽

Exploratory Study ◽

Germ Cell Tumors ◽

Lymphocyte Subpopulations ◽

Lower Percentage ◽

Control Group ◽

Testicular Cancer Survivors

Abstract 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 (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/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.

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Collateral damage: Molecular aging and p16INK4a senescence protein in testicular cancer survivors treated with chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.548 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 548-548

Author(s):

Maria Teresa Bourlon ◽

Hugo Eduardo Velazquez ◽

Luis Arturo Orozco Bello ◽

Juan Hinojosa ◽

Ricardo Rios-Corzo ◽

...

Keyword(s):

Testicular Cancer ◽

Cancer Survivors ◽

Mononuclear Cells ◽

Germ Cell Tumors ◽

Lymphocyte Subpopulations ◽

Lower Percentage ◽

Immune Risk Profile ◽

P16ink4a Expression ◽

Molecular Aging ◽

Testicular Cancer Survivors

548 Background: Cytotoxic chemotherapy can cure patients with 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 patients exposed to chemotherapy. Methods: Case-control study of testicular cancer survivors (TCS) treated with chemotherapy (≥3 BEP cycles, disease-free ≥ 3 months) matched by age with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16INK4a expression was measured using real-time polymerase chain reaction, and the 2-ΔΔCt method was used for the p16INK4a expression analysis. Groups were compared with Mann-Whitney U test. Results are expressed as median (IQR) unless otherwise indicated. Results: We included 15 cases and 15 controls. Mean age 32.5 yo (24-54), mean time since last chemo 49.5 months (3-192). TCS had a lower percentage of CD3+ (62 (57-68) vs 72 (65-82) p = 0.026) and CD4+ (35 (27-41) vs 42 (38-53) p = 0.013) cells in total lymphocytes. TCS also had a lower % of naïve CD4+ (32 (15-44) vs 39 (32-55) p = 0.041), CD4+CD28+ (90 (85-97) vs 98 (95-99) p = 0.029) and CD8+ naïve (15 (8-26) vs 27 (22-42) p = 0.023) cells. TCS had an increased % of memory CD4+ (18 (13-26) vs 9 (6-11) p = 0.001) and memory CD19+ B cells (76 (62-88) vs 70 (64-79) p = 0.004). The relative expression of p16INK4a in CD3+ cells was higher in TCS compared to controls (1.29±0.36 vs 0.85±0.54; p = 0.035). Conclusions: TCS showed an increase in the expression of the aging biomarker p16INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory and CD28- cells. This phenomenon is believed to contribute to the development of an immune risk profile in the elderly, associated with an increased rate of infections and a diminished effect of vaccines. This is the first time this finding is reported in TCS. Further studies are warranted to define the clinical implications of this alteration.

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Psychological Needs Satisfaction, Self-Rated Health and the Mediating Role of Exercise Among Testicular Cancer Survivors

American Journal of Men s Health ◽

10.1177/15579883211012601 ◽

2021 ◽

Vol 15 (2) ◽

pp. 155798832110126

Author(s):

Anika R. Petrella ◽

Catherine M. Sabiston ◽

Madison F. Vani ◽

Andrew Matthew ◽

Daniel Santa Mina

Keyword(s):

Mental Health ◽

Testicular Cancer ◽

Cancer Survivors ◽

Psychological Needs ◽

Basic Psychological Needs ◽

Exercise Behavior ◽

Physical And Mental Health ◽

Self Rated Health ◽

Needs Satisfaction ◽

Testicular Cancer Survivors

Exploring tenets of basic psychological needs theory, the objective of this study was to examine the association between psychological needs satisfaction, exercise behavior, and physical and mental health among testicular cancer survivors. The present study investigated whether psychological needs satisfaction was directly associated with increased self-rated health, and if this relationship was mediated by engagement in exercise. Testicular cancer survivors ( N = 135; Mage = 32.45; SD = 7.63) self-reported current psychological needs satisfaction, exercise behavior, and perceived global physical and mental health during routine oncology visits. Associations were examined using path analysis. Psychological needs satisfaction was a positive correlate of both self-rated physical and mental health in this sample, and exercise mediated the association between needs satisfaction and self-rated physical health. This study supports the assumptions underpinning basic psychological needs theory in this unique clinical population. Based on the findings, exercise engagement represents one mechanism associated with perceived health after cancer. Supportive care interventions should aim to enhance satisfaction of psychological needs and investigate exercise as a mechanism underpinning the relationship between needs satisfaction and perceived health in testicular cancer survivors.

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7112 POSTER DISCUSSION Early Diagnosis of Androgen Deprivation Syndrome in Testicular Cancer Survivors – an Audit of 1155 Patients in the West Midlands

European Journal of Cancer ◽

10.1016/s0959-8049(11)72027-5 ◽

2011 ◽

Vol 47 ◽

pp. S508

Author(s):

M. Karina ◽

P. Hutton ◽

N. Jaiswal ◽

M. Khan ◽

R. Smith ◽

...

Keyword(s):

Early Diagnosis ◽

Testicular Cancer ◽

Cancer Survivors ◽

Androgen Deprivation ◽

The West ◽

West Midlands ◽

Testicular Cancer Survivors

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A study of coping in long-term testicular cancer survivors

Psychology Health & Medicine ◽

10.1080/13548501003623955 ◽

2010 ◽

Vol 15 (2) ◽

pp. 146-158 ◽

Cited By ~ 17

Author(s):

Robert Rutskij ◽

Torfinn Gaarden ◽

Roy Bremnes ◽

Olav Dahl ◽

Arnstein Finset ◽

...

Keyword(s):

Testicular Cancer ◽

Cancer Survivors ◽

Testicular Cancer Survivors

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IMMU-49. DYNAMIC CHANGES AND PROGNOSTIC VALUE OF PERIPHERAL BLOOD LYMPHOCYTE SUBSETS IN INTRACRANIAL GERM CELL TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noab196.408 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi103-vi104

Author(s):

Hairong Wang ◽

Cheng-Cheng Guo ◽

Hongyu Chen ◽

Yang Qun-ying ◽

Zhong-ping Chen

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Germ Cell ◽

Peripheral Blood ◽

B Lymphocyte ◽

Germ Cell Tumors ◽

T Helper ◽

Tumor Treatment ◽

Dynamic Changes ◽

Intracranial Germ Cell Tumors

Abstract OBJECTIVE This study was designed to retrospectively analyze the dynamic changes of peripheral blood lymphocyte subsets and prognosis among patients with intracranial germ cell tumors. METHODS A total of 150 intracranial germ cell tumors patients diagnosed between June 2011 till November 2019 were retrospectively investigated. Peripheral blood total T lymphocytes (CD3+) percentage, T helper/inducible lymphocytes(CD3+CD4+)percentage, T inhibitory/toxic lymphocytes (CD3+CD8+) percentage, B lymphocyte (CD19+) percentage, NK lymphocyte (CD3/CD16+CD56+) percentage, regulatory T cells (CD4+CD25+,CD8+CD25+), and T helper/toxic lymphocyte ratio (CD4+/CD8+ ratio) were quantified by flow cytometry analysis. Clinical information was extracted from the database in Sun Yat-sen University Cancer Center and survival data was confirmed through outpatient visits and telephone follow-up. RESULTS T lymphocytes population was increased after anti-tumor treatment, with significant difference of total T lymphocytes (CD3+), inhibitory/toxic T cells (CD3+CD8+) and regulatory T cells (CD4+CD25+ and CD8+CD25+), (p=0.008, p=0.000, p=0.008 and p=0.001 respectively), while B lymphocytes(CD19+) decreased after chemotherapy(p=0.003). The dynamic levels of T lymphocyte and B lymphocyte subpopulation after chemotherapy did not present significant differences between gender, age, and locations of tumors (p >0.05), except CD4+CD25+ T cells in younger children (age< 16 years older) increased significantly than the elder (age >16), p=0.04. Patients with increased CD19+ B cells presented significant suboptimal outcomes compared with the no increased (p=0.024). Similarly, increased CD3+ T cells, CD3+CD8+ T cells, CD4+CD25+ T cells reduced the risk of death (p=0.006, p=0.019, p=0.042 respectively). Multivariate Cox Regression analysis showed: increased CD19+ B cells, p=0.04, HR=1.688, 95%CI=1.025-2.779. CONCLUSION After anti-tumor treatment, cell-mediated immunity activated, enhanced, and dominated in anti-tumor response. An increased level of CD19+ subsets was an independent predictor for inferior overall survival. Systemic circulating T cells immunity played an important role and mediating antitumor responses may pave the road for new immunity strategies.

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