Macrophage-regulatory T cell immune circuits shape the pre-metastatic niche
8 affiliations
- 1Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, University of Jordan, Amman 11942, Jordan
- 2Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman 11942, Jordan
- 3Department of Pharmacology and Toxicology, College of Pharmacy, Al Farahidi University, Baghdad 10070, Iraq
- 4Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka 560027, India
- 5Department of Medical Oncology, IMS and SUM Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India
- 6Department of Biomedical Engineering, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu 600119, India
- 7Department of Biotechnology, University Institute of Biotechnology, Chandigarh University, Mohali, Punjab 140413, India
- 8Department of Surgical Diseases No. 2, Samarkand State Medical University, Samarkand 140100, Uzbekistan
Abstract
The pre-metastatic niche (PMN) is a tumor-conditioned immunosuppressive microenvironment that forms in distant organs prior to metastatic colonization. Macrophages and regulatory T cells (Tregs) play central roles in its formation and function. Tumor-derived exosomes and soluble factors reprogram macrophages into M2-like states, leading to extracellular matrix (ECM) remodeling, increased angiogenesis, vascular leakiness, and fibrotic niche formation. Simultaneously, Tregs are recruited and expanded through pathways involving myeloid-derived suppressor cells (MDSCs), S100 calcium-binding protein A8/A9 (S100A8/A9), receptor for advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), as well as fibroblast-derived exosomal C-C motif chemokine ligand 1 (CCL1)-C-C chemokine receptor type 8 (CCR8) signaling. Cytokines from macrophages suppress natural killer (NK) and cluster of differentiation 8-positive (CD8⁺) T-cell cytotoxicity, facilitating immune evasion. The interaction between macrophages and Tregs creates self-reinforcing suppressive circuits that define the metastatic boundaries and dictate the fate of disseminated tumor cells toward dormancy or growth. This review summarizes the core mechanisms by which macrophages and Tregs mediate PMN formation, highlights the critical role of exosomes in macrophage reprogramming and niche boundary establishment, and discusses targeted therapeutic strategies and translational challenges.
Related
- Macrophage immunometabolism in osteoporosis: an emerging regulatory axis linking metabolic–polarization coupling to therapeutic targets
- Recurrent hypermotif regulatory circuits in developmental programs
- Cross-regulatory sRNA networks shape adaptive stress responses in Staphylococcus aureus: RsaC and RsaOI regulate galactose metabolism and cell wall homeostasis
- Direct cortical feedforward and feedback pathways differentially shape visual responses and selectively engage looped circuits
- Aberrant microglial responses shape hypothalamic circuits in anorexia nervosa
BibTeX
@article{abuhassan2026macrophageregulatory,
title = {{Macrophage-regulatory T cell immune circuits shape the pre-metastatic niche}},
author = {Qamar Abuhassan and Ghaleb Oriquat and Waleed K. Abdulsahib and R. Roopashree and Priya Priyadarshini Nayak and J. Bethanney Janney and Vipasha Sharma and Xushvakt Umedov},
journal = {Cancer pathogenesis and therapy},
year = {2026},
month = may,
doi = {10.1016/j.cpt.2026.04.003},
url = {https://europepmc.org/article/PMC/PMC13717011},
note = {CC BY},
}
RIS
TY - JOUR
TI - Macrophage-regulatory T cell immune circuits shape the pre-metastatic niche
AU - Qamar Abuhassan
AU - Ghaleb Oriquat
AU - Waleed K. Abdulsahib
AU - R. Roopashree
AU - Priya Priyadarshini Nayak
AU - J. Bethanney Janney
AU - Vipasha Sharma
AU - Xushvakt Umedov
PY - 2026
DA - 2026/05/08
JO - Cancer pathogenesis and therapy
DO - 10.1016/j.cpt.2026.04.003
UR - https://europepmc.org/article/PMC/PMC13717011
AB - The pre-metastatic niche (PMN) is a tumor-conditioned immunosuppressive microenvironment that forms in distant organs prior to metastatic colonization. Macrophages and regulatory T cells (Tregs) play central roles in its formation and function. Tumor-derived exosomes and soluble factors reprogram macrophages into M2-like states, leading to extracellular matrix (ECM) remodeling, increased angiogenesis, vascular leakiness, and fibrotic niche formation. Simultaneously, Tregs are recruited and expanded through pathways involving myeloid-derived suppressor cells (MDSCs), S100 calcium-binding protein A8/A9 (S100A8/A9), receptor for advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), as well as fibroblast-derived exosomal C-C motif chemokine ligand 1 (CCL1)-C-C chemokine receptor type 8 (CCR8) signaling. Cytokines from macrophages suppress natural killer (NK) and cluster of differentiation 8-positive (CD8⁺) T-cell cytotoxicity, facilitating immune evasion. The interaction between macrophages and Tregs creates self-reinforcing suppressive circuits that define the metastatic boundaries and dictate the fate of disseminated tumor cells toward dormancy or growth. This review summarizes the core mechanisms by which macrophages and Tregs mediate PMN formation, highlights the critical role of exosomes in macrophage reprogramming and niche boundary establishment, and discusses targeted therapeutic strategies and translational challenges.
SN - 2097-2563
SN - 2949-7132
ER -