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Immune checkpoint inhibitor (ICI) therapy serves as a standard treatment for advanced or recurrent malignant melanoma. Tumour neoantigenicity is an important factor for the effectiveness of the ICI therapy. However, the absence of reliable biomarkers to predict ICI therapy efficacy remains an unresolved challenge. REV7 is a subunit of mutagenic DNA polymerase ζ and plays a role in generating genetic alterations following DNA damage. In this study, we examined REV7 as a potential predictive biomarker for ICI therapy in melanoma. Using RNA in situ hybridisation, we assessed REV7 expression in melanomas from 42 patients who received ICI therapy. Our analysis revealed that high REV7 expression correlated significantly with improved progression-free survival, durable clinical benefit and favourable clinical outcomes according to response evaluation criteria in solid tumours. These findings suggest that REV7 may be a potential predictive biomarker for ICI therapy response in melanoma.
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http://dx.doi.org/10.1136/jcp-2025-210213 | DOI Listing |
J Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
BMJ Open
September 2025
Department of Gastroenterology, Hepatology, Infectious Diseases and Intoxication, University Hospital Heidelberg, Heidelberg, Germany.
Introduction: Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade.
View Article and Find Full Text PDFPharmacoeconomics
September 2025
Department of Pharmacy, Uppsala University, Box 580, 751 23, Uppsala, Sweden.
Background: Immune checkpoint inhibitors (ICIs) are clinically beneficial but associated with high costs that represent a growing challenge for healthcare budgets and may affect affordability, especially in resource-limited settings. Moreover, the healthcare sector is a significant source of greenhouse gas emissions, and medication-related waste-such as that from vial-based therapies-has been identified as a contributing factor. Alternative dosing strategies could reduce the environmental and financial impact of ICI therapy while maintaining clinical safety and efficacy.
View Article and Find Full Text PDFCancer Med
September 2025
Department of Pulmonary Medicine, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Background: The prognosis of small-cell lung cancer (SCLC) remains poor, particularly in patients with extensive-stage SCLC. The IMpower133 and CASPIAN trials revealed the efficacy of immune checkpoint inhibitors (ICIs) in extensive-stage SCLC patients with good performance status (PS). The aim of this study was to investigate the efficacy of ICIs in patients with poor PS.
View Article and Find Full Text PDFJ Immunother Precis Oncol
August 2025
Department of Medicine, Sylvester Comprehensive Cancer Center/University of Miami, Miami, FL, USA.
The combination of targeted therapies and immunotherapies for advanced and metastatic sarcomas has been proposed owing to the enhanced effect of antiangiogenic therapies on the tumor microenvironment. We found eight studies published to date assessing the effectiveness of combined multitargeted vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors with immune checkpoint inhibitors (ICIs) in sarcoma. It is difficult to draw conclusions owing to limited data and primarily single-arm studies, although initial literature appears promising and requires further study.
View Article and Find Full Text PDF