Roles for Inflammation and Regulatory T Cells in Colon Cancer

Abstract

Risk for developing cancer rises substantially as a result of poorly regulated inflammatory responses to pathogenic bacterial infections. Anti-inflammatory CD4+ regulatory cells (TREG) function to restore immune homeostasis during chronic inflammatory disorders. It seems logical that TREG cells would function to reduce risk of inflammation-associated cancer in the bowel by down-regulating inflammation. It is widely believed, however, that TREG function in cancer mainly to suppress protective anticancer inflammatory responses. Thus roles for inflammation, TREG cells, and gut bacteria in cancer are paradoxical and are the subject of controversy. Our accumulated data build upon the “hygiene hypothesis” model in which gastrointestinal (GI) infections lead to changes in TREG that reduce inflammation-associated diseases. Ability of TREG to inhibit or suppress cancer depends upon gut bacteria and IL-10, which serve to maintain immune balance and a protective anti-inflammatory TREG phenotype. However, under poorly regulated pro-inflammatory conditions, TREG fail to inhibit and may instead contribute to a T helper (Th)-17-driven procarcinogenic process, a cancer state that is reversible by down-regulation of inflammation and interleukin (IL)-6. Consequently, hygienic individuals with a weakened IL-10– and TREG–mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated inflammation and show more frequent inflammation-associated cancers. Taken together, these data help explain the paradox of inflammation and TREG in cancer and indicate that targeted stimulation of TREG may promote health and significantly reduce risk of cancer.

973 Relationship of EMAST and Microsatellite Instability Among Patients With Rectal Cancer

“…There is a wellestablished association between tumorigenesis and inflammation as suggested in numerous studies. [29][30][31] Given this, it would be of great interest to ascertain if the association with inflammation demonstrated here with EMAST does also lead to tumorigenesis, either primarily through downregulation of specific mismatch repair genes as shown previously in our lab 9 or secondarily via frameshift mutations of specific genes containing such tetranucleotide repeats in their sequences. It is our hope that this preliminary study demonstrating the high prevalence of EMAST would foster increased research that might help clarify the biological significance of EMAST.…”

Colorectal Cancer Progression Is Associated with Accumulation of Th17 Lymphocytes in Tumor Tissues and Increased Serum Levels of Interleukin-6

“…Chronic low-grade inflammation, a fundamental characteristic of aging, might be associated with an increased risk of tumorigenesis in older populations. Th17 cells have been implicated to be associated with the carcinogenic inflammatory process of colorectal cancer (Erdman and Poutahidis 2010). These cells may persist or promote the disease by generating inflammatory cytokines, such as IL-17A.…”

Neutrophil-to-Lymphocyte Ratio, Plateletto- Lymphocyte Ratio, and Red Blood Cell Distribution Width as New Biomarkers in Patients with Colorectal Cancer

“…However, the risk for colorectal cancer increase owing to increasing proinflammatory cytokines such as TNF-α, IL-6, and IL-17 and decreasing IL-10 because of the effect of T lymphocytes in chronic inflammation (18). RDW, which measures the complete blood count parameter and the size difference of red blood cells, increases with increases in interleukin, a proinflammatory mediator, and cytokines such as TNF-α.…”