ArticleCell research2019
Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade.
Article in Cell research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04866862 (A Single Arm, Open Label, Phase II, Exploratory Study of Fruquitinib Combined With Camrelizumab in Non MSI-H / dMMR Refractory Colorectal Cancer.), which is not on this map. Cited by 172 papers, 1 of them a synthesis that pooled it.
What it found
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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.
A Single Arm, Open Label, Phase II, Exploratory Study of Fruquitinib Combined With Camrelizumab in Non MSI-H / dMMR Refractory Colorectal Cancer.
Who cites it
172 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
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- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Inflammatory bone marrow microenvironment impairs the therapeutic effect of daratumumab-lenalidomide in multiple myeloma.Biomarker research · 2026Article
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- Striking the right balance with type I interferon signalling in cancer.Nature reviews. Cancer · 2026Review
- Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Beyond suppression: the paradox of JAK inhibitors as amplifiers of cancer immunotherapy.Nature reviews. Immunology · 2026Review
- Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma.Molecular oncology · 2026Article
- HE4 drives PD-L1 expression in myeloid cells via IFN-γR-JAK-STAT3 signaling to promote tumor immune evasion.Cell reports. Medicine · 2026Article
- Phase 1b study of ABBV-368, tilsotolimod, budigalimab, and nab-paclitaxel in patients with recurrent/metastatic head and neck squamous cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Harnessing the Microbiome in Cancer Immunotherapy: Regulation, Prediction, and Therapeutic Targeting.Annual review of immunology · 2026Review
- Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy.Nature reviews. Cancer · 2026Review
- PD-1 suppresses CAR signaling by forming the inhibitory signalosome colocalizing to CAR microclusters.Communications biology · 2026Article
- Dissecting the impact of Controlling Nutritional Status (CONUT) score on survival outcomes and immune-inflammatory profiles in patients with advanced NSCLC undergoing first-line immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Single-cell transcriptome analysis reveals regulatory programs associated with tumor resistance during immunotherapy in colorectal cancer.International journal of surgery (London, England) · 2026Article
- Beyond the tumor microenvironment: a hierarchical immune-circuit model of immune checkpoint blockade resistance.Frontiers in oncology · 2026Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 10 institutions in 6 countries.
Funding
Abstract
PD-1 blockade represents a major therapeutic avenue in anticancer immunotherapy. Delineating mechanisms of secondary resistance to this strategy is increasingly important. Here, we identified the deleterious role of signaling via the type I interferon (IFN) receptor in tumor and antigen presenting cells, that induced the expression of nitric oxide synthase 2 (NOS2), associated with intratumor accumulation of regulatory T cells (Treg) and myeloid cells and acquired resistance to anti-PD-1 monoclonal antibody (mAb). Sustained IFNβ transcription was observed in resistant tumors, in turn inducing PD-L1 and NOS2 expression in both tumor and dendritic cells (DC). Whereas PD-L1 was not involved in secondary resistance to anti-PD-1 mAb, pharmacological or genetic inhibition of NOS2 maintained long-term control of tumors by PD-1 blockade, through reduction of Treg and DC activation. Resistance to immunotherapies, including anti-PD-1 mAb in melanoma patients, was also correlated with the induction of a type I IFN signature. Hence, the role of type I IFN in response to PD-1 blockade should be revisited as sustained type I IFN signaling may contribute to resistance to therapy.
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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.