The hypoxic ECM and neutrophils in MIBC immunotherapy resistance
Child, F. Lunj, S. Gough, J. Humphries, M. J. Biolatti, L. V. Hoskin, P. J. Choudhury, A. Quiles, C. G.
Child, F.
Lunj, S.
Gough, J.
Humphries, M. J.
Biolatti, L. V.
Hoskin, P. J.
Choudhury, A.
Quiles, C. G.
Abstract
Immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) have improved survival for patients with different types of solid tumour. However, clinical response in patients with muscle-invasive bladder cancer (MIBC) is limited, with only 20-30% demonstrating a sustained response. An improved understanding of ICI mechanisms and robust biomarkers will increase efficacy and enable patient stratification in MIBC. Hypoxia (low oxygen tension) and neutrophil infiltration are prevalent in MIBC and are associated with immunotherapy resistance. Hypoxia-associated extracellular matrix (ECM) remodelling can induce pro-tumour or anti-tumour neutrophil polarization through biomechanical and biochemical signalling. Hypoxia-associated ECM mechanisms alter neutrophil recruitment, polarization, activation and affect T cell-centric immunotherapies. However, the specific mechanisms by which hypoxia, ECM and neutrophils confer immunotherapy resistance in MIBC are not yet fully understood. ICI resistance could be overcome by targeting specific ECM remodelling-related and neutrophil-related pathways to elicit durable and efficacious responses in 70-80% of patients with MIBC who are currently non-responsive to ICIs.
Description
Date
2025
Publisher
Collections
Keywords
Type
Article
Citation
Child F, Lunj S, Gough J, Humphries MJ, Biolatti LV, Hoskin PJ, et al. The hypoxic ECM and neutrophils in MIBC immunotherapy resistance. Nat Rev Urol. 2025 Oct 13. PubMed PMID: 41083779. Epub 2025/10/14. eng.