title: Immune senescence and cancer in elderly patients: results from an exploratory study.
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 ≥70year old cancer patients.
  
  
  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.
authors.affiliation: Medical Oncology Unit II, Istituto Oncologico Veneto (IOV), IRCCS, Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Falci
authors.forename: Ketty
authors.initials: K
authors.lastname: Gianesin
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sergi
authors.forename: Silvia
authors.initials: S
authors.lastname: Giunco
authors.forename: Irene
authors.initials: I
authors.lastname: De Ronch
authors.forename: Sara
authors.initials: S
authors.lastname: Valpione
authors.forename: Caterina
authors.initials: C
authors.lastname: Soldà
authors.forename: Pasquale
authors.initials: P
authors.lastname: Fiduccia
authors.forename: Sara
authors.initials: S
authors.lastname: Lonardi
authors.forename: Marisa
authors.initials: M
authors.lastname: Zanchetta
authors.forename: Sonia
authors.initials: S
authors.lastname: Keppel
authors.forename: Antonella
authors.initials: A
authors.lastname: Brunello
authors.forename: Valeria
authors.initials: V
authors.lastname: Zafferri
authors.forename: Enzo
authors.initials: E
authors.lastname: Manzato
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D015577:Geriatric Assessment; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D012307:Risk Factors; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019098:Telomerase
keywords: ADL; Activities of Daily Living; CGA; CIRS-CI; CIRS-SI; CMV; Cancer; Cumulative Illness Rating Scale-Comorbidity Index; Cumulative Illness Rating Scale-Severity Index; Cytomegalovirus; Elderly; GDS; Geriatric Depression Scale; IADL; Immune senescence; Instrumental Activities of Daily Living; MMSE; MNA; MPI; Mini Mental Status Examination; Mini Nutritional Assessment; PBMC; RTE; RU; SPMSQ; Short Portable Mental Status Questionnaire; T-cell receptor rearrangement excision circle; T/S; TREC; Telomerase activity; Telomere length; Thymic output; comprehensive geriatric assessment; multidimensional prognostic index; peripheral blood mononuclear cells; recent thymic emigrant; relative units; telomere/single-copy gene