Non-Genetic Biomarkers in Merkel Cell Carcinoma: Prognostic Implications and Predictive Utility for Response to Anti-PD-(L)1 Immune Checkpoint Inhibitors.

Merkel cell carcinoma (MCC) is a skin cancer that arises due to either Merkel cell polyomavirus infection (MCPyV) or ultraviolet (UV) radiation exposure, presenting primarily in the head and neck region of fair-skinned males. The recent success of PD-(L)1 immune checkpoint inhibitors (ICIs) in locally advanced/metastatic MCC, with an objective response rate (ORR) around 50% and improved survival, as a first-line treatment has moved ICIs to the forefront of therapy for MCC and generated interest in identifying biomarkers to predict clinical response. The MCC tumour microenvironment (TME) contains various components of the adaptive and innate immune system.

A Decadal Exploration of Cutaneous Adverse Effects of FDA-Approved Cardiovascular Medications: Insights from 2013 to 2023.

Given the high prevalence of cardiovascular disease in the United States, there is a critical need for new medications to improve outcomes of these diseases. The U.S.

Exploring the Association Between Atopic Dermatitis and Malignancy: A Comprehensive Review with Therapeutic Strategies.

Atopic dermatitis (AD) is a prevalent dermatologic condition affecting both children and adults, and the debate surrounding its association as either a risk or protective factor for malignancies has garnered significant attention. Proposed mechanisms suggest that AD may act protectively against cancer formation through chronic immune system activation or create an inflammatory state conducive to cancer development. This review discusses the relationship between AD and various skin cancers, solid tumors, and hematologic malignancies.

CPT1A-mediated fatty acid oxidation confers cancer cell resistance to immune-mediated cytolytic killing.

Although tumor-intrinsic fatty acid β-oxidation (FAO) is implicated in multiple aspects of tumorigenesis and progression, the impact of this metabolic pathway on cancer cell susceptibility to immunotherapy remains unknown. Here, we report that cytotoxicity of killer T cells induces activation of FAO and upregulation of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme of FAO in cancer cells. The repression of CPT1A activity or expression renders cancer cells more susceptible to destruction by cytotoxic T lymphocytes.

Stressed target cancer cells drive nongenetic reprogramming of CAR T cells and solid tumor microenvironment.

The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR).