ArticleThe Journal of experimental medicine2025
Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- AGTR1 signaling contributes to tumor immunity and therapy response in non-small cell lung cancer.Molecular therapy. Oncology · 2026Article
- Hypoxia increases the activity of oncolytic adenoviruses through HIF-2α-stimulated E1A expression.Signal transduction and targeted therapy · 2026Article
- Bacterial-based cancer therapy: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Integrated hypoxia and metabolic gene signature to predict clinical outcomes and therapeutic vulnerabilities in lung adenocarcinoma.Journal of thoracic disease · 2026Article
- Advances in translational lung cancer research in 2025: a narrative review.Translational lung cancer research · 2026Review
- Clinico-molecular characteristics and enhanced efficacy of immune checkpoint inhibitors in TP53-mutated advanced biliary tract cancer.Journal of gastroenterology · 2026Article
- Endoplasmic reticulum stress in antitumor immunity and immunotherapy resistance: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Gαi1 and Gαi3 mediate IL-11-induced signal transduction and are potential therapeutic targets for LUAD.Cell death & disease · 2026Article
- Nano-in-Micro GelMA depots assist electro-thermal-immuno orchestral treatment for solid triple negative breast tumor.Materials today. Bio · 2026Article
- Deficiencies in the Fanconi anemia or homologous recombination pathway enhance the antitumor effects of the hypoxia-activated prodrug CP-506.Molecular therapy. Oncology · 2026Article
- Roles of Cellular Neighborhoods in Lung Cancer.Journal of Cancer · 2026Review
- Anti-angiogenic therapies in cancer: from endogenous inhibitors to bispecific VEGF x PD-(L)1 antibodies.Frontiers in immunology · 2026Review
- Survival patterns and mutation profiles in never- and light-smokers with stage IV NSCLC.BMC cancer · 2025Article
- Targeted NAT10 Degradation by PROTAC NP1192 Suppresses Hypoxia-Adaptive Glycolysis and Reinvigorates CD8ACS central science · 2025Article
- Review
- Survival Outcomes in EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases: Kaplan-Meier and Cox Regression Analyses Across Treatment Stages.The clinical respiratory journal · 2025Article
- Prognostic Significance of Modified Shine and Lal Index in Patients with Non-Small Cell Lung Cancer Undergoing Surgical Resection.Biomedicines · 2025Article
- Adenosine receptors on the immuno-oncology expressway: TIME, perspectives, and translation.Frontiers in immunology · 2025Review
- Overcoming resistance to immune checkpoint inhibitor in non-small cell lung cancer: the promise of combination therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Despite the established use of immune checkpoint inhibitors (ICIs) to treat non-small cell lung cancer (NSCLC), only a subset of patients benefit from treatment and ∼50% of patients whose tumors respond eventually develop acquired resistance (AR). To identify novel drivers of AR, we generated murine Msh2 knock-out (KO) lung tumors that initially responded but eventually developed AR to anti-PD-1, alone or in combination with anti-CTLA-4. Resistant tumors harbored decreased infiltrating T cells and reduced cancer cell-intrinsic MHC-I and MHC-II levels, yet remained responsive to IFNγ. Resistant tumors contained extensive regions of hypoxia, and a hypoxia signature derived from single-cell transcriptional profiling of resistant cancer cells was associated with decreased progression-free survival in a cohort of NSCLC patients treated with anti-PD-1/PD-L1 therapy. Targeting hypoxic tumor regions using a hypoxia-activated pro-drug delayed AR to ICIs in murine Msh2 KO tumors. Thus, this work provides a rationale for targeting tumor metabolic features, such as hypoxia, in combination with immune checkpoint inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.