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Immune senescence and cancer in elderly patients: Results from an exploratory study
Authors:Cristina Falci  Ketty Gianesin  Giuseppe Sergi  Silvia Giunco  Irene De Ronch  Sara Valpione  Caterina Soldà  Pasquale Fiduccia  Sara Lonardi  Marisa Zanchetta  Sonia Keppel  Antonella Brunello  Valeria Zafferri  Enzo Manzato  Anita De Rossi  Vittorina Zagonel
Institution:1. Medical Oncology Unit II, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy;2. Section of Oncology and Immunology, Department of Surgery, Oncology and Gastroenterology-DiSCOG, University of Padova, Padova, Italy;3. Department of Medicine-DiMED, Geriatric Section, University of Padova, Padova, Italy;4. Immunology and Molecular Oncology, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy;5. Medical Oncology Unit I, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy
Abstract:

Background

The challenge of immune senescence has never been addressed in elderly cancer patients. This study compares the thymic output and peripheral blood telomere length in ≥ 70 year old cancer patients.

Patients and methods

Fifty-two elderly cancer patients and 39 age-matched controls without personal history of cancer were enrolled. All patients underwent a Comprehensive Geriatric Assessment (CGA), from which a multidimensional prognostic index (MPI) score was calculated. Peripheral blood samples were studied for naïve and recent thymic emigrant (RTE) CD4+ and CD8+ cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels, telomere length and telomerase activity in peripheral blood cells were quantified by real-time PCR.

Results

The percentages of CD8+ naïve and CD8+ RTE cells and TREC levels were significantly lower in cancer patients than in controls (p = 0.003, p = 0.004, p = 0.031, respectively). Telomere lengths in peripheral blood cells were significantly shorter in cancer patients than in controls (p = 0.046) and did not correlate with age in patients, whereas it did in controls (r = − 0.354, p = 0.031). Short telomere (≤ median)/low TREC (≤ median) profile was associated with higher risk of cancer (OR = 3.68 95% CI 1.22–11.11]; p = 0.021). Neither unfitness on CGA nor MPI score were significantly related to thymic output or telomere length in either group.

Conclusions

Immune senescence is significantly worse in elderly cancer patients than in age-matched controls. The low thymic output and the shorter telomeres in peripheral blood cells of cancer patients may reflect a pre-existing condition which facilitates the onset of malignancies in elderly people.
Keywords:CGA  comprehensive geriatric assessment  MPI  multidimensional prognostic index  RTE  recent thymic emigrant  TREC  T-cell receptor rearrangement excision circle  RU  relative units  ADL  Activities of Daily Living  IADL  Instrumental Activities of Daily Living  SPMSQ  Short Portable Mental Status Questionnaire  MMSE  Mini Mental Status Examination  CIRS-CI  Cumulative Illness Rating Scale-Comorbidity Index  CIRS-SI  Cumulative Illness Rating Scale-Severity Index  GDS  Geriatric Depression Scale  MNA  Mini Nutritional Assessment  T/S  telomere/single-copy gene  PBMC  peripheral blood mononuclear cells  CMV  Cytomegalovirus
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