Biomarkers related to immunosenescence: relationships with therapy and survival in lung cancer patients

Abstract

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. 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. 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 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. 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.