Immune Suppression and Colorectal Cancer

C. Evans; A. G. Dalgleish; D. Kumar

Disclosures

Aliment Pharmacol Ther. 2006;24(8):1163-1177. 

In This Article

TGF-β

Transforming growth factor (TGF)-β is a multifunctional peptide factor, which regulates cell proliferation, differentiation, adhesion, apoptosis, angiogenesis, extracellular matrix accumulation and other cellular processes.[159] Generally, TGF-β inhibits the growth of normal intestinal epithelial cells but can switch to a growth stimulator with tumour progression and enhance malignant transformation.[160] In the later stages of tumour development TGF-β is actively secreted by tumour cells or stromal cells and contributes to cell growth, invasion, metastasis, and decrease in host antitumour immune responses.[161]

The main target of TGF-β's immunosuppressive actions are T lymphocytes,[161] inhibiting their proliferation,[162] differentiation and maturation.[161] It inhibits tumour-specific CD8 immune responses[163,164] and the killing ability of TIL.[162] TGF-β also inhibits the expression of co-stimulatory molecules on DC[165] and alters their distribution within the body.[117] It has an inhibitory effect on macrophages; inhibiting the production of TNF-α, H2O2 and NO whilst stimulating IL-10 formation,[161] NK cytotoxicity; downregulating an NK-activating receptor, NKG2D,[166] and LAKs.[162]

Active and/or latent expression of TGF-β can occur from colon carcinoma cells[167] with higher plasma concentrations of TGF-β measured in patients with colorectal cancer.[168,169,170] Levels of TGF-β correlate with Dukes' staging[168] and have been related to tumour vascular invasion, lymph node involvement and distant metastases.[160] TGF-β inhibits the actions of immunotherapies including cancer vaccines[171] and blockade of its activity inhibits tumour progression and promotes rejection in experimental models.[172,173,174]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....