Immune Suppression and Colorectal Cancer

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

Disclosures

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

In This Article

'Counter Attack' Hypothesis

Fas-mediated apoptosis of lymphocytes normally serves an immunoregulatory role. It has been suggested that colorectal tumours can exploit this lymphocyte death programme by expressing FasL. This may enable colon tumours to mount a 'Fas counterattack' against antitumour lymphocytes.[130] FasL is both expressed on the surface of colon tumour cells[140,141] and released from the cells in microvesicles.[142] Expression has been linked with tumour progression,[143] diminished TIL[144] and a higher incidence of lymph node invasion and distant metastases.[145] However, contradictory studies have been unable to demonstrate expression of FasL on colorectal tumour cells[131,146] and one study reported that gene transfer of FasL into the colon carcinoma CT26 (which does not express Fas) induced potent inflammatory reactions with regression of the malignancies.[147] It may be that immune suppression is the result of an indirect mechanism and is not dependent solely on signalling through the Fas/FasL pathway.[148] It is also possible that the Fas-mediated apoptosis of infiltrating lymphocytes is a consequence of T-cell activation.[149]

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