Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 37 min ago
Peer-reviewedCC BY 4.0Frontiers in Immunology

NLRP3 signalling in NSCLC: distinguishing expression, inflammasome activation and context-dependent function

  • Xin Wang1,2
  • Yangli Zhong1,3
  • Bin Pan2,4
  • Kai Yang1,4
  • Hongmei Tan2,4
  • Ling Huang1,5
  • Xi Li1,6
6 affiliations
  1. 1School of Clinical Medicine, Chengdu Medical College
  2. 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College
  3. 3Department of Dermatology, The First Affiliated Hospital of Chengdu Medical College
  4. 4Key Laboratory of Geriatric Respiratory Diseases of Sichuan Higher Education Institutes
  5. 5Department of Pharmacy, The First Affiliated Hospital of Chengdu Medical College
  6. 6Department of Integrated Traditional Chinese and Western Medicine, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College
Read full textPDFDOICite

Abstract

Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality despite advances in targeted therapy and immune checkpoint blockade. NLRP3-associated inflammation has attracted increasing interest in NSCLC, yet interpretation of the available evidence remains challenging because molecular expression, inflammasome activation, cytokine processing, pyroptotic execution and pathway dependence are frequently considered together. Here, we present a structured narrative review and an evidence framework that separates the biological event directly measured from the level of NLRP3-specific mechanistic support, while independently considering cellular source, disease relevance and treatment context. Current evidence indicates that NLRP3-specific mechanistic dependence in NSCLC has been demonstrated only in selected experimental settings, particularly treatment-conditioned macrophage models. Treatment-naïve human evidence reveals compartment-specific inflammasome-associated responses in alveolar macrophages and peripheral leukocytes but does not establish NLRP3 dependence. Tumour-cell studies support treatment-induced inflammasome- and pyroptosis-associated phenotypes, although causal attribution to NLRP3 is often incomplete. Single-cell and spatial studies mainly identify NLRP3-related transcriptional states or candidate microenvironmental niches and cannot, by themselves, demonstrate functional inflammasome activation or NLRP3-dependent interactions. Clinical trials targeting IL-1β provide evidence for downstream inflammatory modulation but do not directly evaluate NLRP3 inhibition. Overall, current evidence supports context-dependent NLRP3-associated biology in NSCLC rather than a uniform biomarker or therapeutic target. Future studies integrating cell-resolved localisation, activation-specific measurements, pathway perturbation and longitudinal validation are required to determine whether clinically relevant NLRP3-dependent states can be reproducibly identified.

Related

  1. Sublethal disulfide stress facilitates TLR2-dependent NLRP3 inflammasome activation and pyroptosis in leukemia cells.
    Shoko Hosojima, Shenghui Zhi, Yamato Tanabe +4
    Cell death & diseasePeer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMCDOAJPMC
  2. Molecular mechanisms of NLR proteins in inflammasome activation
    Yichao Liu, Kexin Ji, Liman Zhang
    Communications BiologyPeer-reviewedCC BY-NC-ND 4.0Full textMolecular biology & gene regulationCrossrefEurope PMCDOAJ
  3. Bergapten Alleviates Periodontitis by Suppressing NLRP3 Inflammasome Activation via Mitophagy-Induced Disruption of NEK7-NLRP3 Interaction.
    Xiangbin Jia, Yuzhao Wang, Jiao Cao +6
    Antioxidants (Basel, Switzerland)Peer-reviewedCC BYFull textMolecular biology & gene regulationEurope PMC
  4. Possible Links Between PM2.5-Induced NLRP3 Inflammasome Activation and Its Role in Lung Cancer Progression and Drug Resistance
    Thanaphat Worawichitchaikun, Pitchapa Wantanachaisaeng, Teerapat Teeppaibul +1
    International Journal of Molecular SciencesPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationCrossrefEurope PMC
  5. O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ
    Xunhu Gu, Yufeng Chen, Lili Zheng +6
    Experimental NeurobiologyPeer-reviewedCC BY-NC 4.0Full textMolecular biology & gene regulationPMC

Cite

BibTeXRIS
BibTeX
@article{wang2026nlrp3,
  title = {{NLRP3 signalling in NSCLC: distinguishing expression, inflammasome activation and context-dependent function}},
  author = {Xin Wang and Yangli Zhong and Bin Pan and Kai Yang and Hongmei Tan and Ling Huang and Xi Li},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1983973},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983973/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - NLRP3 signalling in NSCLC: distinguishing expression, inflammasome activation and context-dependent function
AU  - Xin Wang
AU  - Yangli Zhong
AU  - Bin Pan
AU  - Kai Yang
AU  - Hongmei Tan
AU  - Ling Huang
AU  - Xi Li
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1983973
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983973/full
AB  - Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality despite advances in targeted therapy and immune checkpoint blockade. NLRP3-associated inflammation has attracted increasing interest in NSCLC, yet interpretation of the available evidence remains challenging because molecular expression, inflammasome activation, cytokine processing, pyroptotic execution and pathway dependence are frequently considered together. Here, we present a structured narrative review and an evidence framework that separates the biological event directly measured from the level of NLRP3-specific mechanistic support, while independently considering cellular source, disease relevance and treatment context. Current evidence indicates that NLRP3-specific mechanistic dependence in NSCLC has been demonstrated only in selected experimental settings, particularly treatment-conditioned macrophage models. Treatment-naïve human evidence reveals compartment-specific inflammasome-associated responses in alveolar macrophages and peripheral leukocytes but does not establish NLRP3 dependence. Tumour-cell studies support treatment-induced inflammasome- and pyroptosis-associated phenotypes, although causal attribution to NLRP3 is often incomplete. Single-cell and spatial studies mainly identify NLRP3-related transcriptional states or candidate microenvironmental niches and cannot, by themselves, demonstrate functional inflammasome activation or NLRP3-dependent interactions. Clinical trials targeting IL-1β provide evidence for downstream inflammatory modulation but do not directly evaluate NLRP3 inhibition. Overall, current evidence supports context-dependent NLRP3-associated biology in NSCLC rather than a uniform biomarker or therapeutic target. Future studies integrating cell-resolved localisation, activation-specific measurements, pathway perturbation and longitudinal validation are required to determine whether clinically relevant NLRP3-dependent states can be reproducibly identified.
SN  - 1664-3224
ER  -