ArticleCancer cell2023
Simultaneous targeting of PD-1 and IL-2Rβγ with radiation therapy inhibits pancreatic cancer growth and metastasis.
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Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56citing papers in PubMed
17.5field-weighted citation impact, top 1% of its field
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Who cites it
56 citing papers in PubMed, 74 citations in OpenAlex.
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Spatially fractionated radiotherapy and immunotherapy: a synergistic strategy for systemic anti-tumor immunity.Journal of translational medicine · 2026Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Immuno-cytotoxic convergence: integrating antibody‒drug conjugates and immunofusion proteins to overcome resistance in gastrointestinal cancers.Journal of hematology & oncology · 2026Review
- Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy.Nature reviews. Cancer · 2026Review
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Targeting IL-12 for pancreatic cancer immunotherapy: advances in delivery strategies and clinical translation.Frontiers in immunology · 2026Review
- The multidimensional regulatory network of the PD‑1/PD‑L1 axis in the esophageal squamous cell carcinoma microenvironment: Implications for novel combination therapies and precision immunotherapy (Review).Oncology reports · 2026Review
- Targeting CD39 in combination with IL-2/anti-IL-2 complexes enhances cytotoxic immunity and limits tumor progression.Frontiers in immunology · 2026Article
- The central role of radiotherapy in remodeling the tumor immune microenvironment: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- FUT2 enhances anti-tumor immunity in pancreatic cancer radiotherapy by driving FBXO2-mediated degradation of NR2F2.Cell death & disease · 2025Article
- Mechanistic and functional characterization of ABTB2 as a novel target for pancreatic cancer therapy.Molecular therapy. Oncology · 2025Article
- Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7Oncoimmunology · 2025Article
- Review
- Orchestrating T and NK cells for tumor immunotherapy via NKG2A-targeted delivery of a de novo designed IL-2Rβγ agonist.Drug delivery · 2025Article
- Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.Oncoimmunology · 2025Review
- NFAT5 Regulates IL8 to Promote Cell Growth and Migration in Non-Small Cell Lung Cancer.Thoracic cancer · 2025Article
- Lymphatic metastasis in pancreatic cancer: from bedside to bench and back.Cancer metastasis reviews · 2025Review
- Progress in the Application of Marine Polysaccharide Drug Delivery Systems in Tumor Immunotherapy: Multiple Mechanisms and Material Forms.Marine drugs · 2025Review
- Regulatory T cells in cancer anti-PD-(L)1 therapy.Human cell · 2025Review
Corrections and comments
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Authors and funding
26 authors at 2 institutions in 2 countries.
Miles PiperDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Maureen HoenDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Laurel B DarraghDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Microbiology and Immunology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Michael W KnitzDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Diemmy NguyenDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Jacob GadwaDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Greta DuriniRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Idil KarakocRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Abby GrierDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
Brooke NeupertDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Benjamin Van CourtDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Khalid N M AbdelazeemDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Justin YuDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Nicholas A OlimpoDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Sophia CorboDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Richard Blake RossDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Tiffany T PhamDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Molishree JoshiDepartment of Pharmacology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Ross M KedlDepartment of Microbiology and Immunology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA.
Anthony J SaviolaDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
Maria AmannRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Pablo UmañaRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Laura Codarri DeakRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Christian KleinRoche Innovation Center Zurich, Roche Pharma Research and Early Development (pRED), Schlieren, Switzerland.
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA.
Sana D KaramDepartment of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Microbiology and Immunology, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: sana.karam@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USRoche (Switzerland) · CH
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MTreating recurrent HNSCC with radiation and dual TGF-Beta/PD-L1.P50CA261605 · NCI · UNIVERSITY OF COLORADO DENVER · PI JIMENO, ANTONIO, WANG, XIAO-JING · 2021 to 2025
$10.1MInstitutional Training in Otolaryngology ResearchT32DC012280 · NIDCD · UNIVERSITY OF COLORADO DENVER · PI Yuri Agrawal, Sue C. Kinnamon · 2013 to 2026
$3.4MRole of EphB4-ephrin-B2 interaction in regulating crosstalk between cancer cell and vascular tumor microenvironment in head and neck cancerR01DE028282 · NIDCR · UNIVERSITY OF COLORADO DENVER · PI KARAM, SANA D · 2019 to 2023
$2.4MMulti-Modal Optical/ microCT system for Colorado Animal Imaging ResourceS10OD027023 · OD · UNIVERSITY OF COLORADO DENVER · PI SERKOVA, NATALIE J. · 2020 to 2020
$733kNCI NIH HHS P30 CA046934NCI NIH HHS P50 CA261605NIDCD NIH HHS T32 DC012280NIDCR NIH HHS R01 DE028282NIH HHS S10 OD027023
Abstract
In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rβ and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival, along with a profound increase in tumor-infiltrating CD8
Indexed as
Carcinoma, Pancreatic DuctalPancreatic NeoplasmsCD8-Positive T-LymphocytesHumansImmunotherapyInterleukin-2Interleukin-2 Receptor alpha SubunitProgrammed Cell Death 1 ReceptorInterleukin-2Interleukin-2 Receptor alpha SubunitProgrammed Cell Death 1 Receptorantigen specificitycancer immunotherapycytotoxic T lymphocyteimmune memorymetabolomicsmetastasisNK cellsT cell stemnessTregstumor immunology
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