T Cell Subpopulations in Healthy Elderly and Lung Cancer Patients: Insights from Cuban Studies

Abstract

The senescence of the immune system and the risk of cancer increase with aging. Age itself entails changes in the immune system, which are related to a decrease in thymic output of naïve lymphocytes, an accumulation of chronic antigenic load, notably chronic viral infections such as cytomegalovirus (CMV), and replicative senescence of lymphocytes. These changes could eventually contribute to cancer risk and affect the response to cancer treatment. However, several confounding factors make it difficult to draw a picture of causal relationships. Studies in diverse human populations could contribute to clarify these complex relationships. Here, we summarize the current knowledge about the senescence of the T cells, the relationship with CMV infection, cancer, and cancer treatment. We also review the results of a series of studies performed in Cuba whose population is characterized by the unusual combination of long life expectancy and high antigenic load, including high seroprevalence of CMV, typical of tropical countries. Although immunosenescence affects almost all components and functions of the immune response, its most salient feature is a decrease in numbers and proportions of naïve CD8+ T lymphocytes and an accretion of terminally differentiated CD8+ T lymphocytes. These features were confirmed by the Cuban studies, but interestingly a clear gender effect also appeared. Moreover, as aging is a global phenomenon, a fast increase in elderly with malignancies is expected; therefore, the evaluation of patient’s immune status would support the decision of treating them with immunotherapy and predict the efficacy of such treatments, thereby improving benefits for the patients.

Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen

“…Changes in peripheral T-cell compartments may be age-related as previously reported for naive and T EMRA CD8 + T cells in other studies 32,33 . Thus, we performed correlation analysis between age and flow cytometry data in FL patients before treatment.…”

Age-related changes in T lymphocytes of patients with head and neck squamous cell carcinoma

“…Accordingly, the frequency of naïve T cells decreases, while the frequency of memory and effector cells increases with age. As described by Saavedra et al, the number and proportion of naïve CD8 + lymphocytes may be reduced due to a decreased output of naïve lymphocytes with increasing age while terminally differentiated CD8 + T cells accumulate [31]. The frequency of tumorinfiltrating CD8 + T c cells, on the other hand, remained stable in our cohort of elderly cancer patients.…”

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

“…Similarly, the secretion of another cytokine, IL-12, by dendritic cells was reduced in older adults which caused decreased INF-gamma secretion by T cells thereby impeding its cytotoxic activity [ 78 ]. Although the number of Naïve T cells was decreased in older cohorts, possibly due to reduction in the size of the thymus [ 79 ], the number of terminally differentiated CD8 T cell populations was found to be increased in lung cancer patients [ 80 ]. The frequency of Treg cells was also significantly increased in older people with HNSCC.…”