ArticleThe Journal of clinical investigation2020
A tumor-intrinsic PD-L1/NLRP3 inflammasome signaling pathway drives resistance to anti-PD-1 immunotherapy.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 1 of them a synthesis that pooled it.
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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
172 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.Annals of medicine · 2026Pooled it
- Tumor NLRP3 amplification promotes immunotherapy resistance by inhibiting STAT1 signaling and MHC class I expression.The Journal of clinical investigation · 2026Article
- Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.Cancers · 2026Review
- Two inflammasomes as tumour markers for nonmelanocytic skin cancer: new hopes for early detection and targeted therapy.Skin health and disease · 2026Review
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- The Aberrant Activation of NLRP3 in Microsatellites Stability Colon Cancer Promotes M2 Macrophage Polarization Based on the TCGA Database and Tissue Microarray Analysis.Cancer reports (Hoboken, N.J.) · 2026Article
- PD-L1 cell-intrinsic signals limit immune activation during cutaneous vaccinia virus infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Integrative dual ctDNA 5mC/5hmC methylomics and clonal reconstruction infer tumor transcription and resistance phenotypes in metastatic prostate cancer.Research square · 2026Article
- CD300ld blockade overcomes PMN-MDSC-mediated vaccine resistance in advanced tumors.Journal for immunotherapy of cancer · 2026Article
- Resistance mechanisms and reversal strategies of PD-1/PD-L1 inhibitors in melanoma.Frontiers in pharmacology · 2026Review
- NLRP3 inflammasomes at the ARDS-cancer interface: mechanisms and translational hypotheses.Frontiers in immunology · 2026Review
- Targeting innate immunity in cancer: mechanistic foundations, therapeutic vaccination, and clinical translation.Frontiers in immunology · 2026Review
- NLRPs and tumor: research progress from molecular mechanisms to clinical applications.Oncogene · 2026Review
- Aging modulation of the immune system and immunotherapy efficacy in cancer.Frontiers in immunology · 2026Review
- The NLRP3 inflammasome in gynecological cancers: a double-edged sword shaping the immune microenvironment and immunotherapy response.Frontiers in immunology · 2026Review
- First-line PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for advanced esophageal and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of randomized controlled trials.Journal of gastrointestinal oncology · 2025Article
- Changes in PD-1 expression on T lymphocyte subsets and related immune indicators before and after definitive chemoradiotherapy for esophageal squamous cell carcinoma.Annals of medicine · 2025Article
- Molecular mechanisms and regulation of inflammasome activation and signaling: sensing of pathogens and damage molecular patterns.Cellular & molecular immunology · 2025Review
- Targeting SPHK1 in macrophages remodels the tumor microenvironment and enhances anti-PD-1 immunotherapy efficacy in colorectal cancer liver metastasis.Cancer communications (London, England) · 2025Article
- Tumor Microenvironmental Dynamics in Shaping Resistance to Therapeutic Interventions in Melanoma: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain-containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti-PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti-PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.
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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.