Telomeres are at the non-coding ends of linear chromosomes. Through a complex 3-dimensional structure, they protect the coding DNA and ensure appropriate separation of chromosomes. Aging is characterized by a progressive shortening of telomeres, which compromises their structure and function. Because of their protective function for genomic DNA, telomeres appear to play an important role in the development and progression of many age-related diseases, such as cardiovascular disease (CVD), malignancies, dementia, and osteoporosis. Despite substantial evidence that links telomere length with these conditions, the nature of these observations remains insufficiently understood. Therefore, future studies should address the question of causality. Furthermore, analytical methods should be further improved with the aim to provide informative and comparable results. This review summarize the actual knowledge of telomere biology and the possible implications of telomere dysfunction for the development and progression of age-related diseases. Furthermore, we provide an overview of analytical techniques for the measurement of telomere length and telomerase activity.

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.

Introduction: Epirubicin is a common adjuvant treatment for breast cancer. It is mainly eliminated after glucuronidation through uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7). The present study aimed to describe the impact of theUGT2B7^His268Tyrpolymorphism on invasive disease-free survival in breast cancer patients after epirubicin treatment.Methods: This is a pharmacogenetic study based on samples collected from 745 breast cancer patients of the AustrianTumor of breast tissue:Incidence,Genetics, andEnvironmentalRisk factors (TIGER) cohort who did not present metastases at baseline. This cohort included 205 women with epirubicin-based combination chemotherapy, 113 patients having received chemotherapy without epirubicin and 427 patients having received no chemotherapy at all. Of the epirubicin-treated subgroup, 120 were subsequently treated with tamoxifen. For all womenUGT2B7^His268Tyrwas genotyped. Invasive disease-free survival was assessed using Kaplan-Meier and Cox's proportional hazard regression analysis.Results: Among the 205 epirubicin-treated patients, carriers of twoUGT2B7^268Tyralleles had a mean invasive disease-free survival of 8.6 (95% confidence interval (CI) 7.9 to 9.3) years as compared to 7.5 (95% CI 6.9 to 8.0) years in carriers of at least oneUGT2B7^268Hisallele (adjusted hazard ratio (HR) = 2.64 (95% CI 1.22 to 5.71);P= 0.014). In addition, the impact of theUGT2B7^His268Tyrpolymorphism became even more pronounced in patients subsequently treated with tamoxifen (adjusted HR = 5.22 (95% CI 1.67 to 26.04);P= 0.015) whereas no such difference in invasive disease-free survival was observed in patients not receiving epirubicin.Conclusions: Breast cancer patients carrying theUGT2B7^268Tyr/Tyrgenotype may benefit most from adjuvant epirubicin-based chemotherapy. These results warrant confirmation in further studies.

Aminotransaminases, including aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT), are strongly involved in cancer cell metabolism and have been associated with prognosis in different types of cancer. The purpose of the present study was to evaluate the prognostic significance of the pre-treatment AST/ALT ratio in a large European cohort of patients with oral and oropharyngeal squamous cell cancer (OOSCC). Data from 515 patients treated for OOSCC at a tertiary academic center from 2000–2017 were retrospectively analyzed. Levels of AST and ALT were measured prior to the start of treatment. Uni- and multivariate Cox regression analyses were applied to evaluate the prognostic value of the AST/ALT ratio for cancer-specific survival (CSS) and overall survival (OS), survival rates were calculated. Univariate analyses showed a significant association of the AST/ALT ratio with CSS (hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.38–2.12; p < 0.001) and OS (HR 1.69, 95% CI 1.41–2.02; p < 0.001). In multivariate analysis, the AST/ALT ratio remained an independent prognostic factor for CSS and OS (HR 1.45, 95% CI 1.12–1.88, p = 0.005 and HR 1.42, 95% CI 1.14–1.77, p = 0.002). Applying receiver operating characteristics (ROC) curve analysis, the optimal cut-off level for the AST/ALT ratio was 1.44, respectively. In multivariate analysis, an AST/ALT ratio > 1.44 was an independent prognostic factor for poor CSS and OS (HR 1.64, 95% CI 1.10–2.43, p = 0.014 and HR 1.55, 95% CI 1.12–2.15; p = 0.008). We conclude that the AST/ALT ratio is a prognostic marker for survival in OOSCC patients and could contribute to a better risk stratification and improved oncological therapy decisions.

Atherosclerosis (AS) leading to myocardial infarction and stroke remains worldwide the main cause for mortality. Vulnerable atherosclerotic plaques are responsible for these life-threatening clinical endpoints. Atherosclerosis is a chronic, complex, inflammatory disease with interactions between metabolic dysfunction, dyslipidemia, disturbed microbiome, infectious triggers, vascular, and immune cells. Undoubtedly, the immune response is a most important piece of the pathological puzzle in AS. Although macrophages and T cells have been the focus of research in recent years, B cells producing antibodies and regulating T and natural killer (NKT) cell activation are more important than formerly thought. New results show that the B cells exert a prominent role with atherogenic and protective facets mediated by distinct B cell subsets and different immunoglobulin effects. These new insights come, amongst others, from observations of the effects of innovative B cell targeted therapies in autoimmune diseases like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). These diseases associate with AS, and the beneficial side effects of B cell subset depleting (modifying) therapies on atherosclerotic concomitant disease, have been observed. Moreover, the CANTOS study (NCT01327846) showed impressive results of immune-mediated inflammation as a new promising target of action for the fight against atherosclerotic endpoints. This review will reflect the putative role of B cells in AS in an attempt to connect observations from animal models with the small spectrum of the thus far available human data. We will also discuss the clinical therapeutic potency of B cell modulations on the process of AS.