Immune Suppression and Colorectal Cancer

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

Disclosures

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

In This Article

HLA-G Expression

HLA-G is a low polymorphic non-classical MHC class I expressed in several different tumours including renal cell carcinoma, melanoma, breast carcinoma, ovarian carcinoma and colorectal cancer.[150,151,152,153,154] Its expression may allow partially or non-histocompatible cells to escape the host's immune system through inhibiting NK and CTL cells mediated lysis binding and interacting with the inhibitory receptors ILT2 and ILT4.[155,156] The HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E, which inhibits NK lysis[157] plus secreted HLA-G5 binds to CD8 inducing Fas/FasL-mediated apoptosis in activated CD8+ lymphocytes.[156]

Embryological studies have demonstrated that membrane-bound HLA-G (mHLA-G) expressed on trophoblasts is one of the key factors in regulating cytokine balance by shifting the Th1/Th2 balance towards Th2 polarization, a favourable milieu for the maintenance of pregnancy[158] which, as previously discussed, is a beneficial environment for the survival of tumours and may be created by tumour mHLA-G expression.

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