title: Biomarkers related to immunosenescence: relationships with therapy and survival in lung cancer patients.
abstract: OBJECTIVE
  There are well-known alterations occurring within the immune system with aging. Collectively, these changes are known as immunosenescence. The incidence of malignancies also increases with age. The aim of this study was to determine the presence of immunosenescence biomarkers in non-small cell lung cancer (NSCLC) patients and to evaluate some of them as predictive biomarkers of CIMAvax-EGF cancer vaccine efficacy.
  
  
  METHODS
  Sixty-six NSCLC patients, vaccinated or not with CIMAvax-EGF cancer vaccine, and 37 age-matched controls were enrolled. Peripheral blood samples were studied for CD19+, CD4+, CD8+, CD28-, CD57+ and CD45RA+ subpopulations by flow cytometry.
  
  
  RESULTS
  Absolute count of CD19+ and the CD4/CD8 ratio were significantly lower in NSCLC patients than in age-paired controls, while highly differentiated T cells increased in NSCLC patients treated with platinum-based chemotherapy. Using Cox regression, we were able to dichotomize the patient population according to biomarkers. Vaccinated patients with frequency <24 % of CD8 + CD28- T cells, >40 % of CD4 T cells and CD4/CD8 ratio higher than two at the beginning of immunotherapy achieved a 20-month increase in median survival regarding control patients.
  
  
  CONCLUSIONS
  Distribution of lymphocyte subsets was influenced by cancer and chemotherapy in NSCLC patients. CD19 + B cells decrease by cancer disease and not by chemotherapy, and CD28- subpopulations increase by chemotherapy and not by cancer. The proportion of CD8 + CD28- T cells, CD4+ T cells and CD4/CD8 ratio can be used as predictive biomarkers of CIMAvax-EGF efficacy in NSCLC patients and thereby could, be a useful tool for a personalized treatment.
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba. danays@cim.sld.cu.
authors.forename: Danay
authors.initials: D
authors.lastname: Saavedra
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Beatriz
authors.initials: B
authors.lastname: García
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lorenzo-Luaces
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Amnely
authors.initials: A
authors.lastname: González
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Xitlally
authors.initials: X
authors.lastname: Popa
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Karla P
authors.initials: KP
authors.lastname: Fuentes
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Zaima
authors.initials: Z
authors.lastname: Mazorra
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Tania
authors.initials: T
authors.lastname: Crombet
authors.affiliation: Hermanos Ameijeiras Hospital, Havana, Cuba.
authors.forename: Elia
authors.initials: E
authors.lastname: Neninger
authors.affiliation: Clinical Immunology Department, Center of Molecular Immunology, 216 St, Corner 15, PO Box 16040, Havana, Cuba.
authors.forename: Agustin
authors.initials: A
authors.lastname: Lage
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D005260:Female; D006801:Humans; D000068884:Immunosenescence / Q000502:physiology*; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008297:Male; D016019:Survival Analysis
chemical_list: D015415:Biomarkers
keywords: Cancer vaccine; Immunosenescence; Immunosenescence markers; Non-small cell lung cancer