Characterisation of clinical response and transcriptional profiling of proliferating CD8 T cells in the blood of cancer patients after PD-1 monotherapy or combination therapy.

Objective: Immune checkpoint inhibitors (ICI) that block the programmed cell death 1 (PD-1) pathway have shown promise with limited benefit. We and others have shown in small patient cohorts that an early proliferative CD8 T-cell response in the blood may be predictive of clinical response. However, these studies lack detailed analyses and comparisons between monotherapy and combination therapies.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

An early precursor CD8 T cell that adapts to acute or chronic viral infection.

This study examines the origin and differentiation of stem-like CD8+ T cells that are essential for sustained T cell immunity in chronic viral infections and cancer and also play a key role in PD-1 directed immunotherapy. These PD-1+ TCF-1+ TOX+ stem-like CD8+ T cells, also referred to as precursors of exhausted T cells, have a distinct program that allows them to adapt to chronic antigen stimulation. Using the mouse model of chronic LCMV infection we found that virus specific stem-like CD8+ T cells are generated early (day 5) during chronic infection suggesting that this crucial fate commitment occurs irrespective of infection outcome.

Treatment strategies to reduce cardiovascular risk in persons with chronic kidney disease and Type 2 diabetes.

Chronic kidney disease (CKD) is a prevalent and progressive condition associated with significant mortality and morbidity. Diabetes is a common cause of CKD, and both diabetes and CKD increase the risk of cardiovascular disease (CVD), the leading cause of death in individuals with CKD. This review will discuss the importance of early detection of CKD and prompt pharmacological intervention to slow CKD progression and delay the development of CVD for improving outcomes.