The vasculature of tumours is highly abnormal and dysfunctional. Consequently, immune effector cells have an impaired ability to penetrate solid tumours and often exhibit compromised functions. Normalization of the tumour vasculature can enhance tissue perfusion and improve immune effector cell infiltration, leading to immunotherapy potentiation. However, recent studies have demonstrated that the stimulation of immune cell functions can also help to normalize tumour vessels. In this Opinion article, we propose that the reciprocal regulation between tumour vascular normalization and immune reprogramming forms a reinforcing loop that reconditions the tumour immune microenvironment to induce durable antitumour immunity. A deeper understanding of these pathways could pave the way for identifying new biomarkers and developing more effective combination treatment strategies for patients with cancer.
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http://dx.doi.org/10.1038/nri.2017.145 | DOI Listing |
Sci Adv
January 2025
The Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).
View Article and Find Full Text PDFPhysiol Rep
January 2025
Developmental Biology and Cancer Research and Teaching Department, University College London, Great Ormond Street Institute of Child Health, London, UK.
Polycystic kidney diseases (PKD) are genetic disorders which disrupt kidney architecture and function. Autosomal recessive PKD (ARPKD) is a rare form of PKD, caused by mutations in PKHD1, and clinically more severe than the more common autosomal dominant PKD (ADPKD). Prior studies have implicated Hedgehog (Hh) signaling in ADPKD, with increased levels of Hh components in experimental ADPKD and reduced cystogenesis following pharmacological Hh inhibition.
View Article and Find Full Text PDFIdecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( = 162) versus cilta-cel ( = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS).
View Article and Find Full Text PDFPlant Mol Biol
January 2025
State Key Laboratory for Crop Stress Resistance and High-Efficiency Production and College of Plant Protection, Northwest A&F University, Yangling, 712100, China.
Psa primarily utilises the type III secretion system (T3SS) to deliver effector proteins (T3Es) into host cells, thereby regulating host immune responses. However, the mechanism by which kiwifruit responds to T3SS remains unclear. To elucidate the molecular reaction of kiwifruit plants to Psa infection, M228 and mutant M228△hrcS strains were employed to inoculate Actinidia chinensis var.
View Article and Find Full Text PDFCancer Immunol Res
January 2025
Baylor College of Medicine, Houston, TX, United States.
Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.
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