Performed in Tübingen at the Center for Medical Research, University of Tübingen, under the supervision of Prof. Dr. Graham Pawelec, the comparative study of SLAS (Singapore Longitudinal Aging Study) / BASE (Berlin Aging Study) aims at analysing the impact of immunosenescence in different societies, with implications for health and longevity.
Croeni Charity supported this initiative with an unrestricted educational research grant which resulted in a joint German-Singaporean research collaboration and several publications, such as:
- Peripheral blood T-cell signatures from high-resolution immune phenotyping of γδ and αβ T-cells in younger and older subjects in the Berlin Aging Study II (Immunity & Ageing, 2015). The term “immunosenescence” is commonly taken to mean age-associated changes in immune parameters hypothesized to contribute to increased susceptibility and severity of the older adult to infectious disease, autoimmunity and cancer. Aging and latent infection with human herpesvirus 5 (Cytomegalovirus, CMV) are thought to be major factors driving the immune system towards immunosenescence, primarily characterized by reduced amounts of naïve T-cells and increased memory T-cells, potentially associated with higher morbidity and mortality. The findings illustrate in detail the strong influence of CMV and age on the abundance and composition of both major compartments, γδ as well as αβ T-cells. However, the mechanisms responsible for the phenotypic alterations in the γδ T-cell compartment require further clarification.
- Phenotypic characterization and prognostic impact of circulating γδ and αβ T-cells in metastatic malignant melanoma (International Journal of Cancer, Volume 138, Issue 3, 2016). This study analyzes associations of γδ T-cell subsets and differentiation stages with survival in Stage IV cancer patients, compared with CD4+ and CD8+ αβ T-cells. For the first time, the findings suggest peripheral blood frequencies of Vδ1+ T-cells as a promising potential prognostic biomarker in melanoma. The reason to determine why higher frequencies of Vδ1+ cells are associated with poorer survival requires further analysis.
- Establishing High Dimensional Immune Signatures from Peripheral Blood via Mass Cytometry in a Discovery Cohort of Stage IV Melanoma Patients (The Journal of Immunology, Volume 198, Issue 2, 2017). The identification of blood-borne biomarkers correlating with melanoma patient survival remains elusive. Novel techniques such as mass cytometry could help to identify melanoma biomarkers, allowing simultaneous detection of up to 100 parameters. This study has employed 38-channel time-of-flight mass cytometry analysis to generate comprehensive immune cell signatures using matrix boolean analysis in a cohort of twenty-eight stage IV melanoma patients and seventeen controls. Clusters of parameters were constructed from the abundance of cellular phenotypes significantly different between patients and controls. An association with superior survival was characterized by a balanced distribution of myeloid-derived suppressor cell-like and APC-like myeloid phenotypes and differentiated NK cells. The results of this study in a discovery cohort of melanoma patients suggest that multifactorial immune signatures have the potential to allow more accurate prediction of individual patient outcome. Further investigation of the identified immune signatures in a validation cohort is now warranted.
- The Role of CMV in Immunosenescence (The Ageing Immune System and Health, 2017). In humans, immunosenescence is characterized by lower numbers and frequencies of naïve T and B cells and higher numbers and frequencies of late-differentiated T cells, especially CD8+ T cells, in the peripheral blood. The latter may be very noticeable, but intriguingly, only in people infected by CMV. This book chapter reviews some of the studies implicating CMV infection in immunosenescence and its consequences for ageing trajectories in humans.