ArticlePharmaceuticals (Basel, Switzerland)2022
Activation of Host-NLRP3 Inflammasome in Myeloid Cells Dictates Response to Anti-PD-1 Therapy in Metastatic Breast Cancers.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Analysis of the NLRP3 inflammasome components expression in triple-negative breast cancer patients with and without BRCA1 mutations.Scientific reports · 2026Article
- NLRPs and tumor: research progress from molecular mechanisms to clinical applications.Oncogene · 2026Review
- Immune system, inflammatory response, and regulated cell death in breast cancer research (Review).Oncology reports · 2026Review
- Innate immune signaling-driven myeloid remodeling in cancer: inflammatory amplification, immune suppression, and therapeutic targeting.Frontiers in immunology · 2026Review
- CTLA-4 and targeted immunotherapy-a key link in the systemic influence of periodontitis: a mini review.Frontiers in dental medicine · 2025Review
- Tumor-infiltrating immune cells state-implications for various breast cancer subtypes.Frontiers in immunology · 2025Review
- Immune evasion and resistance in breast cancer.American journal of cancer research · 2025Review
- Article
- The Role of Inflammasome-Associated Innate Immune Receptors in Cancer.Immune network · 2024Review
- Engineered Immunologic Niche Monitors Checkpoint Blockade Response and Probes Mechanisms of Resistance.Immunomedicine · 2024Article
- An In Silico Investigation of Pharmacological Modulators and Inflammasomes in Glioblastoma Multiforme.Applied biochemistry and biotechnology · 2024Article
- Article
- NLRP3 and cancer: Pathogenesis and therapeutic opportunities.Pharmacology & therapeutics · 2023Review
- The 'speck'-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis.Journal of biomedical science · 2023Review
- Dexamethasone and OLT1177 Cooperate in the Reduction of Melanoma Growth by Inhibiting STAT3 Functions.Cells · 2023Article
- Molecular mechanisms of pyroptosis and its role in anti-tumor immunity.International journal of biological sciences · 2023Review
- "Open Sesame" to the complexity of pattern recognition receptors of myeloid-derived suppressor cells in cancer.Frontiers in immunology · 2023Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Tumor-associated inflammation leads to dysregulated cytokine production that promotes tumor immune evasion and anti-tumor immunity dysfunction. In advanced stage breast cancer, the proinflammatory cytokine IL-1β is overexpressed due to large proportions of activated myeloid cells in the tumor microenvironment (TME). Here, we demonstrate the role of the host nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing 3 (NLRP3) inflammasome in metastatic breast cancer. In vitro, we show that stimulation of THP-1 cells with conditioned media collected from MDA-MB-468 cells induced NLRP3 activation and increased Pdcd1l1 expression. In vivo, mice deficient in NLRP3 orthotopically implanted with metastatic breast cancer cell line (E0771) showed significant reduction in tumor growth (p < 0.05) and increased survival (p < 0.01). Inhibition of NLRP3 with the small molecule OLT1177® reduced expression of Pdcd1l1 (p < 0.001), Casp1 (p < 0.01) and Il1b (p < 0.01) in primary tumors. Furthermore, tumor-bearing mice receiving OLT1177® showed reduced infiltration of myeloid-derived suppressor cells (MDSCs) (p < 0.001) and increased CD8+ T cells (p < 0.05) and NK cells (p < 0.05) in the TME. NLRP3 inhibition in addition to anti-PD-1 treatment significantly reduced tumor growth from the monotherapies (p < 0.05). These data define NLRP3 activation as a key driver of immune suppression in metastatic breast cancers. Furthermore, this study suggests NLRP3 as a valid target to increase efficacy of immunotherapy with checkpoint inhibitor in metastatic breast cancers.
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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.