Immune Suppression and Colorectal Cancer

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


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

In This Article


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]


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