ArticleCancer cell2022
Peroxynitrite in the tumor microenvironment changes the profile of antigens allowing escape from cancer immunotherapy.
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Article in Cancer cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36citing papers in PubMed
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36 citing papers in PubMed, 47 citations in OpenAlex.
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- Self-assembled chemiluminescent nanoprobes based on α,α-dicyanoolefins: leveraging a dioxetane "funnel" for high-contrast inflammation imaging.Chemical science · 2026Article
- Nitration in cancer signaling.Redox biology · 2026Review
- Messing with Signal 1: How Perturbed MHC Class I Antigen Presentation Contributes to Cancer.Cells · 2026Review
- Melanin as a Redox Hub: Linking Energy Flow to Genome Stability and Immune Control.Antioxidants & redox signaling · 2026Review
- From Oxygen to Sulfur: Rhodamine Hydrazide Probes for Peroxynitrite Detection from the Perspective of Theoretical Calculation.Journal of fluorescence · 2026Article
- Cascade-driven nanomotor with self-amplifying necrosis targeting and deep tumor penetration for enhanced type I photodynamic immunotherapy.Materials today. Bio · 2026Article
- Latest advances in nanodrug delivery systems for modulating the immune microenvironment in triple-negative breast cancer.Frontiers in immunology · 2026Review
- From Transient to Metastable: Generation, Characterization, and Biomimetic Reactivity Studies of Well-Defined Heme Peroxynitrite Model Systems.Journal of the American Chemical Society · 2025Article
- Multimodal sensing platform based on MnOMikrochimica acta · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Molecular characterization of NOS3 and SOD1 genes as markers for detecting patients with breast cancer.Molecular biology reports · 2025Article
- Recent Advancement in Fluorescent Probes for Peroxynitrite (ONOOSensors (Basel, Switzerland) · 2025Review
- Phenyl Radical-Mediated Fluorogenic Cyclization for Specific Detection of Peroxynitrite.Analytical chemistry · 2025Article
- The heterogeneity of neutrophils in cancer and its implication for therapeutic targeting.Nature immunology · 2025Article
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Authors and funding
31 authors at 11 institutions in 5 countries.
Evgenii N TcyganovImmunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Emilio SansevieroAstraZeneca, ICC, Early Oncology, Gaithersburg, MD 20878, USA.
Douglas MarvelImmunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Thomas BeerMolecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Hsin-Yao TangMolecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Peter HembachMolecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA.
David W SpeicherMolecular and Cellular Oncogenesis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Qianfei ZhangAstraZeneca, ICC, Early Oncology, Gaithersburg, MD 20878, USA.
Laxminarasimha R DonthireddyImmunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Ali MostafaAstraZeneca, ICC, Early Oncology, Gaithersburg, MD 20878, USA.
Sabina TsyganovaDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vladimir PisarevFederal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow 107031, Russia; Central Institute of Epidemiology, 111123 Moscow, Russia.
Terri LauferDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dmitriy IgnatovMax Planck Unit for the Science of Pathogens, Charitéplatz 1, 10117 Berlin, Germany.
Soldano FerroneDepartment of Surgery, Harvard University, Boston, MA 02114, USA.
Christiane MeyerDepartment of Oncology, University of Lausanne, Lausanne, Switzerland.
Hélène Maby-El HajjamiDepartment of Oncology, University of Lausanne, Lausanne, Switzerland.
Daniel E SpeiserDepartment of Oncology, University of Lausanne, Lausanne, Switzerland.
Sooner AltiokH. Lee Moffitt Cancer Center, Tampa, FL 33612, USA.
Scott AntoniaDuke Cancer Center, Durham, NC 27708, USA.
Xiaowei XuAbramson Cancer Center, Department of Pathology and Molecular Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Wei XuAbramson Cancer Center, Department of Pathology and Molecular Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Cathy ZhengAbramson Cancer Center, Department of Pathology and Molecular Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Lynn M SchuchterDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Ravi K AmaravadiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Tara C MitchellDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Giorgos C KarakousisDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
Zhe YuanGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Luis J MontanerImmunology, Microenvironment, and Metastasis Program, Wistar Institute, Philadelphia, PA 19104, USA.
Esteban CelisGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
Dmitry I GabrilovichAstraZeneca, ICC, Early Oncology, Gaithersburg, MD 20878, USA. Electronic address: dmitry.gabrilovich@astrazeneca.com.
The Wistar Institute · USUniversity of Pennsylvania · USAstraZeneca (United States) · USUniversity of Lausanne · CHAstraZeneca (Netherlands) · NLAugusta University Health · USCentral Research Institute of Epidemiology · RUDuke Medical Center · USHarvard University · USMax Planck Unit for the Science of Pathogens · DEMoffitt Cancer Center · US
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MTumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Luis J Montaner · 1985 to 2026
$75.9MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2008 to 2023
$37.1MTargeting exosomal PDL1 to improve immunotherapyP50CA261608 · NCI · WISTAR INSTITUTE · PI VILLANUEVA, JESSIE · 2021 to 2025
$11.3MTargeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MLipids and Myeloid Cell Function in CancerR01CA165065 · NCI · WISTAR INSTITUTE · PI KAGAN, VALERIAN E, MONTANER, LUIS J · 2012 to 2022
$3.8MAdvancing Cancer Research through Comprehensive Proteomics and Metabolomics AnalysesR50CA221838 · NCI · WISTAR INSTITUTE · PI Hsin-Yao Tang · 2017 to 2026
$2.1MT cell plasticity, fusion proteins and CAR T cell-based immunotherapy of head and neck cancerR01DE028172 · NIDCR · MASSACHUSETTS GENERAL HOSPITAL · PI WANG, XINHUI · 2018 to 2022
$1.9MRegulation of Tumor Microenvironment in CancerR01CA177646 · NCI · WISTAR INSTITUTE · PI ANTONIA, SCOTT J., GABRILOVICH, DMITRY I · 2014 to 2016
$1.1MROLE OF THE HLA ANTIGEN PRESENTING MACHINERY (APM) IN RESISTANCE TO PD-1 AXIS BLOCKADE IN NON-SMALL CELL LUNG CANCERR03CA219603 · NCI · YALE UNIVERSITY · PI FERRONE, SOLDANO, SCHALPER, KURT A · 2019 to 2020
$184kNCI NIH HHS P01 CA114046NCI NIH HHS P30 CA010815NCI NIH HHS P30 CA016520NCI NIH HHS P50 CA174523NCI NIH HHS P50 CA261608NCI NIH HHS R01 CA165065NCI NIH HHS R01 CA177646NCI NIH HHS R03 CA219603NCI NIH HHS R50 CA221838NIDCR NIH HHS R01 DE028172
Abstract
Cancer immunotherapy often depends on recognition of peptide epitopes by cytotoxic T lymphocytes (CTLs). The tumor microenvironment (TME) is enriched for peroxynitrite (PNT), a potent oxidant produced by infiltrating myeloid cells and some tumor cells. We demonstrate that PNT alters the profile of MHC class I bound peptides presented on tumor cells. Only CTLs specific for PNT-resistant peptides have a strong antitumor effect in vivo, whereas CTLs specific for PNT-sensitive peptides are not effective. Therapeutic targeting of PNT in mice reduces resistance of tumor cells to CTLs. Melanoma patients with low PNT activity in their tumors demonstrate a better clinical response to immunotherapy than patients with high PNT activity. Our data suggest that intratumoral PNT activity should be considered for the design of neoantigen-based therapy and also may be an important immunotherapeutic target.
Indexed as
MelanomaTumor MicroenvironmentAnimalsAntigens, NeoplasmEpitopesHistocompatibility Antigens Class IImmunotherapyMiceOxidantsPeptidesPeroxynitrous AcidT-Lymphocytes, CytotoxicAntigens, NeoplasmEpitopesHistocompatibility Antigens Class IOxidantsPeptidesPeroxynitrous Acidcancer immunotherapycytotoxic T cellsmyeloid cellsperoxynitritetumor-associated antigenstumor microenvironment
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