ArticleCancer discovery2017
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations.
Article in Cancer discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 844 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
844 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Heating the Cold: Overcoming Immunotherapy Resistance in Microsatellite-Stable Colorectal Cancer: A Systematic Review.Molecules (Basel, Switzerland) · 2026Pooled it
- Trial
- Phase 1/2 trial of encorafenib, cetuximab, and nivolumab in microsatellite stable BRAFCancer cell · 2025Trial
- Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.Nature medicine · 2024Trial
- The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026Review
- Overcoming melanoma drug resistance: Mechanisms and clinical progress of oncolytic viruses combined with immune checkpoint inhibitors (Review).Oncology reports · 2026Review
- Reprogramming tumor cells with LCOR mRNA nanotherapy to enhance immunotherapy.Molecular oncology · 2026Article
- A20 Inhibits IFN-γ Signaling in Hepatocellular Carcinoma Cells by Binding to STAT1, Compromising Anti-Tumor Immunity.Cancer science · 2026Article
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Resistance to PD-1/PD-L1 blockade: Mechanism and pharmacological strategies.Pharmacological research · 2026Review
- High ZFP36 Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function.Cancer science · 2026Article
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- CAR T Cells Targeting O-Glycosylated Fibronectin Exhibit Potent Cytolytic Activity and Combine with Tumoral Toll-Like Receptor Agonism to Overcome Tumor Resistance.Cancer immunology research · 2026Article
- Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Article
- Recent Advances in Genetically Engineered Mouse Models of Melanoma: Insights into Tumor Initiation and Oncogenic Signaling Pathways.International journal of stem cells · 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
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- Review
784 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors.
Funding
Abstract
Loss-of-function mutations in JAK1/2 can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned that they may also be involved in primary resistance to anti-PD-1 therapy. JAK1/2-inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair-deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK1/2 mutations, which led to a lack of PD-L1 expression upon interferon gamma exposure mediated by an inability to signal through the interferon gamma receptor pathway. JAK1/2 loss-of-function alterations in The Cancer Genome Atlas confer adverse outcomes in patients. We propose that JAK1/2 loss-of-function mutations are a genetic mechanism of lack of reactive PD-L1 expression and response to interferon gamma, leading to primary resistance to PD-1 blockade therapy. SIGNIFICANCE: A key functional result from somatic JAK1/2 mutations in a cancer cell is the inability to respond to interferon gamma by expressing PD-L1 and many other interferon-stimulated genes. These mutations result in a genetic mechanism for the absence of reactive PD-L1 expression, and patients harboring such tumors would be unlikely to respond to PD-1 blockade therapy. Cancer Discov; 7(2); 188-201. ©2016 AACR.See related commentary by Marabelle et al., p. 128This article is highlighted in the In This Issue feature, p. 115.
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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 OpenQuestion graph.