» Articles » PMID: 33299138

Interactions Between Tumor-derived Proteins and Toll-like Receptors

Overview
Journal Exp Mol Med
Date 2020 Dec 10
PMID 33299138
Citations 43
Authors
Affiliations
Soon will be listed here.
Abstract

Damage-associated molecular patterns (DAMPs) are danger signals (or alarmins) alerting immune cells through pattern recognition receptors (PRRs) to begin defense activity. Moreover, DAMPs are host biomolecules that can initiate a noninflammatory response to infection, and pathogen-associated molecular pattern (PAMPs) perpetuate the inflammatory response to infection. Many DAMPs are proteins that have defined intracellular functions and are released from dying cells after tissue injury or chemo-/radiotherapy. In the tumor microenvironment, DAMPs can be ligands for Toll-like receptors (TLRs) expressed on immune cells and induce cytokine production and T-cell activation. Moreover, DAMPs released from tumor cells can directly activate tumor-expressed TLRs that induce chemoresistance, migration, invasion, and metastasis. Furthermore, DAMP-induced chronic inflammation in the tumor microenvironment causes an increase in immunosuppressive populations, such as M2 macrophages, myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). Therefore, regulation of DAMP proteins can reduce excessive inflammation to create an immunogenic tumor microenvironment. Here, we review tumor-derived DAMP proteins as ligands of TLRs and discuss their association with immune cells, tumors, and the composition of the tumor microenvironment.

Citing Articles

NF-κB signaling and the tumor microenvironment in osteosarcoma: implications for immune evasion and therapeutic resistance.

Shi S, Ou X, Liu C, Li R, Zheng Q, Hu L Front Immunol. 2025; 16:1518664.

PMID: 39949765 PMC: 11821961. DOI: 10.3389/fimmu.2025.1518664.


Dengue virus infection: how platelet-leukocyte crosstalk shapes thrombotic events and inflammation.

Amin A, Nikdoust F, Khorram S, Marashi S, Ghanavati P, Ameri F Mol Biol Rep. 2025; 52(1):119.

PMID: 39804486 DOI: 10.1007/s11033-025-10222-x.


CD38 Coordinates with NF-κB to Promote Cochlear Inflammation in Noise-Induced Hearing Loss: the Protective Effect of Apigenin.

Liu D, Sai N, Zhou Y, Yu N, Jiang Q, Sun W Mol Neurobiol. 2024; .

PMID: 39725836 DOI: 10.1007/s12035-024-04675-7.


Differential Expression of Neurodegeneration-Related Genes in SH-SY5Y Neuroblastoma Cells Under the Influence of Cyclophilin A: Could the Enzyme be a Likely Trigger and Therapeutic Target for Alzheimer's Disease?.

Pashaei S, Shabani S, Mohammadi S, Morozova-Roche L, Salari N, Rahimi Z Neurochem Res. 2024; 50(1):47.

PMID: 39636462 DOI: 10.1007/s11064-024-04253-2.


Pancreatic Adenocarcinoma Up-Regulated Factor (PAUF) Transforms Human Monocytes into Alternative M2 Macrophages with Immunosuppressive Action.

Kim Y, Nanda S, Jiang F, Pyo S, Han J, Koh S Int J Mol Sci. 2024; 25(21).

PMID: 39519098 PMC: 11547018. DOI: 10.3390/ijms252111545.


References
1.
Srikrishna G, Freeze H . Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia. 2009; 11(7):615-28. PMC: 2697348. DOI: 10.1593/neo.09284. View

2.
Schirrmacher V, Fournier P . Danger signals in tumor cells: a risk factor for autoimmune disease?. Expert Rev Vaccines. 2010; 9(4):347-50. DOI: 10.1586/erv.10.15. View

3.
Patidar A, Selvaraj S, Sarode A, Chauhan P, Chattopadhyay D, Saha B . DAMP-TLR-cytokine axis dictates the fate of tumor. Cytokine. 2017; 104:114-123. DOI: 10.1016/j.cyto.2017.10.004. View

4.
Zhang J, Shao S, Han D, Xu Y, Jiao D, Wu J . High mobility group box 1 promotes the epithelial-to-mesenchymal transition in prostate cancer PC3 cells via the RAGE/NF-κB signaling pathway. Int J Oncol. 2018; 53(2):659-671. PMC: 6017266. DOI: 10.3892/ijo.2018.4420. View

5.
Choi C, Kang T, Song J, Kim Y, Chung E, Ylaya K . Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is associated with poor prognosis and chemoresistance in epithelial ovarian cancer. Sci Rep. 2018; 8(1):12161. PMC: 6093878. DOI: 10.1038/s41598-018-30582-8. View