Extracellular-vesicle-mediated NLRP3 signaling in cancer

Harish C Chandramoorthy; Raed Obaid Saleh; Viralkumar Mandaliya; Roopashree R; Hanen Mahmod Hulail; Subasini Uthirapathy; Renu Arya; Deepak Nathiya; Dina M R AlKhafaf

doi:10.1016/j.yexcr.2025.114778

Extracellular-vesicle-mediated NLRP3 signaling in cancer

Exp Cell Res. 2025 Oct 1;452(2):114778. doi: 10.1016/j.yexcr.2025.114778. Epub 2025 Sep 29.

Authors

Harish C Chandramoorthy¹, Raed Obaid Saleh², Viralkumar Mandaliya³, Roopashree R⁴, Hanen Mahmod Hulail⁵, Subasini Uthirapathy⁶, Renu Arya⁷, Deepak Nathiya⁸, Dina M R AlKhafaf⁹

Affiliations

¹ Department of Microbiology & Clinical Parasitology, College of Medicine & Central Research Laboratories, King Khalid University, Abha, Saudi Arabia.
² Medical Laboratory Techniques Department, College of Health and Medical Technology, University of Al Maarif, Anbar, Iraq. Electronic address: Dr.raed.obaid@uoa.edu.iq.
³ Marwadi University Research Center, Department of Microbiology, Faculty of Science, Marwadi University, Rajkot, 360003, Gujarat, India.
⁴ Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
⁵ Department of Medical Laboratories Technology, AL-Nisour University College, Baghdad, Iraq.
⁶ Pharmacy Department, Tishk International University, Erbil, Kurdistan Region, Iraq.
⁷ Faculty of Pharmacy, Gokul Global University, Siddhpur, Gujarat, India.
⁸ Department of Pharmacy Practice, Institute of Pharmacy, NIMS University, Rajasthan, Jaipur, India.
⁹ Laboratories Techniques Department, College of Health and Medical Techniques, Al-Mustaqbal University, 51001, Babylon, Iraq.

PMID: 41033571
DOI: 10.1016/j.yexcr.2025.114778

Abstract

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome has recently been characterized as a major player in cancer-related inflammation, tumor progression, immune modulation, and metastasis. The role of extracellular vesicles (EVs), such as exosomes and microvesicles, as active carriers of NLRP3 signaling components is increasingly being recognized, as they modulate the tumor microenvironment as well as distant tissues primed for metastasis. This study will address the diverse roles of EV-mediated NLRP3 signaling in cancer immunopathogenesis, with a particular emphasis on its role in establishing a pre-metastatic niche and immune evasion. Tumor-derived EVs that include NLRP3 as cargo can reprogram stroma and immune cells at secondary sites in the body to support a metabolic role associated with metastatic colonization. While tumor-derived EVs promote extracellular matrix remodeling, angiogenesis, and the recruitment of immune-suppressive cells, this cascade of processes permits the development of a permissive niche for metastatic colonization, and simultaneously impairs anti-tumor immune surveillance. The provided EV-mediated crosstalk also enables tumor cells to evade immune detection through the downregulation of antigen-presenting cells and the activation of immune-suppressive pathways via NLRP3-dependent mechanisms. The molecular mechanisms underlying EV-driven inflammasome signaling could pave the way for the identification of a novel and specific biomarker, in which its modulation could potentially affect the immune system in the tumor microenvironment (TME) and participate in cancer immunopathogenesis. This review highlights the need to dissect further the interactions and context-specific roles of EV-NLRP3 across cancers to identify new therapeutic strategies for preventing metastasis and enhancing immune therapies.

Keywords: Extracellular vesicles; Immune evasion; Inflammation mediators; NLRP3 inflammasome; Neoplasm metastasis; Tumor microenvironment.

Publication types

Review

MeSH terms

Animals
Extracellular Vesicles* / immunology
Extracellular Vesicles* / metabolism
Humans
Inflammasomes / immunology
Inflammasomes / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein* / immunology
NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
Neoplasms* / immunology
Neoplasms* / metabolism
Neoplasms* / pathology
Signal Transduction*
Tumor Microenvironment / immunology

Substances

NLR Family, Pyrin Domain-Containing 3 Protein
Inflammasomes
NLRP3 protein, human