Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer, driven by either Merkel cell polyomavirus (MCPyV) integration or ultraviolet (UV)-induced mutations. In MCPyV-positive tumors, viral T antigens inactivate tumor suppressors pRb and p53, while virus-negative MCCs harbor UV-induced mutations that activate similar oncogenic pathways. Key signaling cascades, including PI3K/AKT/mTOR and MAPK, support tumor proliferation, survival, and resistance to apoptosis. Histologically, MCC consists of small round blue cells with neuroendocrine features, high mitotic rate, and necrosis. The tumor microenvironment (TME) plays a central role in disease progression and immune escape. It comprises a mix of tumor-associated macrophages, regulatory and cytotoxic T cells, and elevated expression of immune checkpoint molecules such as PD-L1, contributing to an immunosuppressive niche. The extracellular matrix (ECM) within the TME is rich in proteoglycans, collagens, and matrix metalloproteinases (MMPs), facilitating tumor cell adhesion, invasion, and interaction with stromal and immune cells. ECM remodeling and integrin-mediated signaling further promote immune evasion and therapy resistance. Although immune checkpoint inhibitors targeting PD-1/PD-L1 have shown promise in treating MCC, resistance remains a major hurdle. Therapeutic strategies that concurrently target the TME—through inhibition of ECM components, MMPs, or integrin signaling—may enhance immune responses and improve clinical outcomes.

Infective endocarditis (IE) is a disease associated with significant morbidity and mortality. It is more commonly caused by Gram-positive cocci, but Gram-positive bacilli may seldom cause the disease. Listeria monocytogenes is an aerobic Gram-positive coccobacillus and a foodborne and opportunistic pathogen most commonly causing gastrointestinal infections, even though bacteremia, sepsis, meningitis, and fetal infections may also occur. Listeria IE has rarely been described, with most reports being case reports or case series. Thus, the characteristics of this disease remain largely unknown. This systematic review aimed to present all published Listeria IE studies and describe their characteristics. A search of PubMed, Scopus, and the Cochrane Library for studies providing information on epidemiology, clinical findings, treatment, and outcome of Listeria IE cases was performed. A total of 54 studies containing data from 62 patients were included. Among all patients, 64.5% were male; the median age was 69 years. Among all patients, 54.8% had a history of a prosthetic valve. The aortic valve was the most commonly affected, followed by the mitral. Fever, heart failure, and embolic phenomena were the most commonly encountered clinical findings. The only isolated species was L. monocytogenes. Antimicrobial resistance was relatively low for aminopenicillins and aminoglycosides, the most commonly used antimicrobials for treating L. monocytogenes IE. Surgery was performed in 27.4% of patients. Mortality was 37.1%. Patients who survived were more likely to have had a prosthetic valve, to have necessitated transesophageal echocardiography for the diagnosis, to have mitral valve IE, and to have had surgical management; however, no factor was identified in a multivariate logistic regression model as an independent factor for overall mortality.