Trial reportScience (New York, N.Y.)2024
Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.
2 registry-linked trialsAbstract readClinical Trial, Phase II
In one paragraph
Trial report in Science (New York, N.Y.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 147 papers.
0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
NCT06966154 phase1 / phase2recruitingnot on this mapstarted 2025, after this paper: background citation
A Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of Tislelizumab in Combination With Golidocitinib and Selinexor for the Treatment of Relapsed/Refractory Natural Killer/T-Cell Lymphoma (NKTCL)
NCT07157306 phase2not yet recruitingnot on this mapstarted 2025, after this paper: background citation
Gecacitinib Combined With Donafenib and PD-1 Inhibitor as Second-Line Therapy for Unresectable Hepatocellular Carcinoma Failed in Immunotherapy, A Phase II Prospective Clinical Study
Who cites it
147 citing papers in PubMed.
- Neoadjuvant PD1 plus CTLA-4 immune checkpoint blockade in surgically resectable recurrent glioblastoma: a randomized surgical window-of-opportunity trial.Nature communications · 2026Trial
- A pilot translational study of neoadjuvant fulvestrant plus abemaciclib in women with advanced low-grade serous carcinoma.Nature communications · 2026Trial
- The current role of immunotherapy in treating nasopharyngeal carcinoma.Human vaccines & immunotherapeutics · 2026Review
- In Vitro Inhibition of STAT5 Signaling Limits CD8+ T-cell Exhaustion and Improves Outcomes in Adoptive T-cell Therapy.Cancer immunology research · 2026Article
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- ATR inhibition induces NF-κB-dependent immunogenicity in Merkel cell carcinoma independent of cGAS-STING.NPJ precision oncology · 2026Article
- Chronic type II interferon promotes tumor growth through mitochondrial RNA-induced type I interferon and prostaglandin synthesis.Science (New York, N.Y.) · 2026Article
- Inflammatory bone marrow microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma.Biomarker research · 2026Article
- The DNA damage response and cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Targeting the JAK/STAT signalling axis in cancer: chemopreventive potential of natural compounds with emerging focus on retinoids.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Optimizing the timing of JAK1 inhibition preserves the anti-tumor efficacy of radioimmunotherapy in lung cancer by preventing T cell exhaustion.Experimental hematology & oncology · 2026Article
- Loss of Kmt2c/d promotes gastric cancer and confers vulnerability to mTORC1 and PD-1 inhibition.The Journal of clinical investigation · 2026Article
- Dermatologic Toxicities Induced by JAK Inhibitors.American journal of clinical dermatology · 2026Review
- Toward precision immunotherapy in recurrent/metastatic head and neck squamous cell carcinoma: lessons from the FOCUS trial.Translational cancer research · 2026Article
- HIF-1α enhances ferroptosis resistance in anaplastic thyroid carcinoma by suppressing ACSL4-mediated lipid metabolic homeostasis.Cellular & molecular biology letters · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy.Nature reviews. Immunology · 2026Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
22 authors.
Divij Mathew *Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-8323-7358
Melina E Marmarelis *Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-2187-3583
Caitlin FoleyDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joshua M BaumlDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Darwin YeParker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-6440-910X
Reem GhinnagowAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0009-0002-8844-8506
Shin Foong NgiowDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-5738-2834
Max KlapholzDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-6527-8722
Soyeong JunDepartment of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-8419-7098
Zhaojun ZhangDepartment of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
Robert ZorcDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-0290-2684
Christiana W DavisDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Maximillian DiehnDepartment of Radiation Oncology and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-2032-0581
Josephine R GilesDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-3713-338X
Alexander C HuangInstitute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0099-0492
Wei-Ting HwangDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-2829-2167
Nancy R ZhangDepartment of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0880-5749
Adam J SchoenfeldDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Erica L CarpenterDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-0735-3605
Corey J LangerDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-8483-6811
E John WherryDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-0477-1956
Andy J MinnInstitute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0003-1418-0906
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI ARTHUR Y KIM · 2009 to 2026
$48.1MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Dario AA Vignali · 2015 to 2026
$30.8MIMMUNOBIOLOGY OF NORMAL AND NEOPLASTIC LYMPHOCYTEST32CA009140 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Malay Haldar, WARREN S PEAR · 1985 to 2026
$16.1MSequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI RILEY, JAMES L. · 2015 to 2019
$12.0MRadiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI MAITY, AMIT, MINN, ANDY J · 2017 to 2022
$11.5MTesting the role of BATF as a pioneer transcription factor in effector T cellsR01AI115712 · NIAID · DANA-FARBER CANCER INST · PI KADOCH, CIGALL, WHERRY, E. JOHN · 2015 to 2019
$2.9MTemporal control of differentiation and epigenetics of Exhausted CD8 T cells by ToxR01AI155577 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2020 to 2024
$2.7MNCI NIH HHS P01 CA210944NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA009140NIAID NIH HHS P01 AI108545NIAID NIH HHS R01 AI115712NIAID NIH HHS R01 AI155577NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950
Abstract
Persistent inflammation driven by cytokines such as type-one interferon (IFN-I) can cause immunosuppression. We show that administration of the Janus kinase 1 (JAK1) inhibitor itacitinib after anti-PD-1 (programmed cell death protein 1) immunotherapy improves immune function and antitumor responses in mice and results in high response rates (67%) in a phase 2 clinical trial for metastatic non-small cell lung cancer. Patients who failed to respond to initial anti-PD-1 immunotherapy but responded after addition of itacitinib had multiple features of poor immune function to anti-PD-1 alone that improved after JAK inhibition. Itacitinib promoted CD8 T cell plasticity and therapeutic responses of exhausted and effector memory-like T cell clonotypes. Patients with persistent inflammation refractory to itacitinib showed progressive CD8 T cell terminal differentiation and progressive disease. Thus, JAK inhibition may improve the efficacy of anti-PD-1 immunotherapy by pivoting T cell differentiation dynamics.
Indexed as
Carcinoma, Non-Small-Cell LungCD8-Positive T-LymphocytesImmune Checkpoint InhibitorsJanus Kinase 1Janus Kinase InhibitorsLung NeoplasmsProgrammed Cell Death 1 ReceptorAnimalsFemaleHumansImmunotherapyMiceImmune Checkpoint InhibitorsJAK1 protein, humanJanus Kinase 1Janus Kinase InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptor
Identifiers
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Read underepoch 390
Registered trials
NCT06966154ClinicalTrials.gov
NCT07157306ClinicalTrials.gov
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 OpenQuestion graph.