Expression profiles and function of IL6 in polymorphonuclear myeloid-derived suppressor cells
Mohammed L Ibrahim1,2,3, Chunwan Lu1,2,4, John D Klement1,2,4
1Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1410 Laney Walker Blvd, Augusta, GA, 30912, USA.
Cancer Immunology, Immunotherapy : CII
|June 4, 2020
Summary
Interleukin-6 (IL6) promotes colon tumor growth, primarily from myeloid-derived suppressor cells. Targeting these IL6-producing cells may suppress tumor progression.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Interleukin-6 (IL6) is an inflammatory cytokine impacting immune and non-immune cells.
- IL6 expression correlates inversely with cancer prognosis, yet IL6 blockade shows limited efficacy.
- Understanding IL6's role in colon cancer is crucial for developing effective therapies.
Purpose of the Study:
- To define IL6 expression profiles in inflammation and colon carcinoma.
- To elucidate the IL6 signaling mechanism in colon carcinoma.
- To investigate the role of IL6 in colon tumor growth and identify therapeutic targets.
Main Methods:
- Analysis of IL6 expression in colon carcinoma and inflammatory conditions.
- Investigation of IL6 signaling pathway activation (STAT3, DNMT1, DNMT3b).
- In vivo studies using IL6 knockout and overexpression models in mice.
Main Results:
- Colonic inflammation induces IL6 primarily in polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs).
- IL6 activates STAT3, up-regulating DNMT1 and DNMT3b in colon tumor cells, indicating an epigenetic mechanism.
- High local IL6 levels are essential for tumor promotion; targeting IL6-expressing PMN-MDSCs shows potential for suppressing colon tumor growth.
Conclusions:
- IL6 up-regulation in colon carcinoma is linked to inflammation and mediated by PMN-MDSCs.
- The IL6-STAT3-DNMT pathway represents a key mechanism in colon tumor promotion.
- Targeting IL6-producing PMN-MDSCs offers a promising therapeutic strategy for colon cancer.
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