Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

Effects of Everolimus in Modulating the Host Immune Responses against Mycobacterium tuberculosis Infection.

The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (P13K/AKT/mTOR) pathway plays a key role in tuberculosis (TB) pathogenesis and infection. While the activity levels of this pathway during active infection are still debated, manipulating this pathway shows potential benefit for host-directed therapies. Some studies indicate that pathway inhibitors may have potential for TB treatment through upregulation of autophagy, while other studies do not encourage the use of these inhibitors due to possible host tissue destruction by Mycobacterium tuberculosis (M. tb) and increased infection risk. Investigating further clinical trials and their use of pathway inhibitors is necessary in order to ascertain their potential for TB treatment. This paper is particularly focused on the drug everolimus, an mTOR inhibitor. One of the first clinical trials sponsored by the Aurum Institute showed potential benefit in using everolimus as an adjunctive therapy for tuberculosis. Infection with tuberculosis is associated with a metabolic shift from oxidative phosphorylation towards glycolysis. The everolimus arm in the clinical trial showed further reduction than the control for both maximal and peak glycolytic activity. Compared with control, those receiving everolimus demonstrated increased lung function through forced expiratory volume in 1 s (FEV1) measurements, suggesting that everolimus may mitigate inflammation contributing to lung damage.

Biomarkers to monitor the prognosis, disease severity, and treatment efficacy in coronary artery disease.

INTRODUCTION: Coronary Artery Disease (CAD) is a prevalent condition characterized by the presence of atherosclerotic plaques in the coronary arteries of the heart. The global burden of CAD has increased significantly over the years, resulting in millions of deaths annually and making it the leading health-care expenditure and cause of mortality in developed countries. The lack of cost-effective strategies for monitoring the prognosis of CAD warrants a pressing need for accurate and efficient markers to assess disease severity and progression for both reducing health-care costs and improving patient outcomes. AREA COVERED: To effectively monitor CAD, prognostic biomarkers and imaging techniques play a vital role in risk-stratified patients during acute treatment and over time. However, with over 1,000 potential markers of interest, it is crucial to identify the key markers with substantial utility in monitoring CAD progression and evaluating therapeutic interventions. This review focuses on identifying and highlighting the most relevant markers for monitoring CAD prognosis and disease severity. We searched for relevant literature using PubMed and Google Scholar. EXPERT OPINION: By utilizing the markers discussed, health-care providers can improve patient care, optimize treatment plans, and ultimately reduce health-care costs associated with CAD management.

Coronary artery disease is a narrowing or blockage of coronary arteries due to the formation of plaque. The main risk factors are inflammation, aging, high cholesterol, shear stress, obesity, and smoking. Narrowing of the arteries results in decreased blood supply (nutrient and oxygen) to the tissue precipitating ischemia presented as angina or myocardial infarction. During ischemic events, there occurs a change in the expression of various molecular and cellular components and increased expressions of many of these factors have been used as biomarkers to diagnose the pathology. Myoglobin, fatty acid-binding proteins, and glycogen phosphorylase isoenzyme BB are early biomarkers, troponin-T and troponin-I are late biomarkers, while creatine kinase-myocardial band is a biomarker in the first 10­12 h for the diagnosis of AMI. However, there is a need for a panel of biomarkers that can help in the prediction, prognosis, and diagnosis of disease progression (atherosclerosis), pre-ischemic and ischemic events, and post-MI periods to design the treatment strategies in a specific and sensitive manner. There is a need for cost-effective sensitive biomarkers that can prevent progression, risk stratify, predict, diagnose, and prevent MI in a timely manner. In this comprehensive review, we discuss the key markers of substantial utility for monitoring coronary artery disease progression and the efficacy of therapeutic intervention among various markers of interest.