ArticleJournal for immunotherapy of cancer2022
Overcoming resistance to αPD-1 of MMR-deficient tumors with high tumor-induced neutrophils levels by combination of αCTLA-4 and αPD-1 blockers.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Pharmacologic Inhibition of PMS2 Induces MMR Deficiency and Response to Immune Checkpoint Blockade.Cancer discovery · 2026Article
- Reprogramming T cell-myeloid crosstalk overcomes immune resistance in colorectal cancer.Cell reports. Medicine · 2026Article
- Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models.The Journal of clinical investigation · 2026Article
- RTP4 Suppresses Colorectal Cancer Progression via MHC-I-Mediated CD8Journal of cellular and molecular medicine · 2025Article
- Targeting neoantigens conserved across organs and species overcomes tumor immune escape.bioRxiv : the preprint server for biology · 2025Article
- T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation.Cancer immunology research · 2025Article
- Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- Case Report: Failed response to anti-PD-1 immunotherapy in a colon cancer patient with high microsatellite instability.Frontiers in oncology · 2025Article
- Lipopolyplex-formulated mRNA cancer vaccine elicits strong neoantigen-specific T cell responses and antitumor activity.Science advances · 2024Article
- Article
- The role of innate immune cells in the colorectal cancer tumor microenvironment and advances in anti-tumor therapy research.Frontiers in immunology · 2024Review
- Genomic instability as a driver and suppressor of anti-tumor immunity.Frontiers in immunology · 2024Review
- Immune escape and resistance to immunotherapy in mismatch repair deficient tumors.Frontiers in immunology · 2023Review
- Predicting immunotherapy outcomes in patients with MSI tumors using NLR and CT global tumor volume.Frontiers in oncology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinical studies have highlighted the efficacy of anti-programmed death 1 (αPD-1) monoclonal antibodies in patients with DNA mismatch repair-deficient (MMRD) tumors. However, the responsiveness of MMRD cancers to αPD-1 therapy is highly heterogeneous, and the origins of this variability remain not fully understood.
methods4T1 and CT26 mouse tumor cell lines were inactivated for the MMRD gene
resultsBy recapitulating mismatch repair deficiency in different mouse tumor models, we revealed that elevated circulating tumor-induced neutrophils (TIN) in hypermutated MMRD tumors hampered response to αPD-1 monotherapy. Importantly, depletion of TIN using αLy-6G antibody reduced Treg cells and restored αPD-1 response. Conversely, targeting Treg cells by αCD25 or αCTLA-4 antibodies limited peripheral TIN accumulation and elicited response in αPD-1-resistant MMRD tumors, highlighting a crosstalk between TIN and Treg cells. Thus, αPD-1+αCTLA-4 combination overcomes TIN-induced resistance to αPD-1 in mice bearing MMRD tumors. Finally, in a cohort of human (high microsatellite instability)/MMRD tumors we revealed that early on-treatment change in the NLR ratio may predict resistance to αPD-1 therapy.
conclusionsTIN countered αPD-1 efficacy in MMRD tumors. Since αCTLA-4 could restrict TIN accumulation, αPD-1+αCTLA-4 combination overcomes αPD-1 resistance in hosts with hypermutated MMRD tumors displaying abnormal neutrophil accumulation.
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