Immune Suppression and Colorectal Cancer

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

Disclosures

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

In This Article

T Cell Loss Of Signalling Molecules

T cells from colorectal cancer patients have atypical T-cell receptors (TCR)[120] with loss of key signalling molecules, such as CD3-associated signal transducing zeta molecule (CD3-ζ)[120,121,122] and p561ck.[123] CD3-ζ is a disulphide-linked homodimer whose cytoplasmic domain, upon phosphorylation, after TCR stimulation, is involved in signal transduction and subsequent activation of T cells.[124] T cells from tumour-bearing mice, lacking CD3-ζ, exhibit impaired cytotoxic function and a decreased ability to mediate an antitumour response.[124] The mechanism for this decrease in CD3-ζ is believed to be the oxidative stress from tumour-derived macrophages upon interaction with T cells.[125]

Loss of CD3-ζ correlates with both the Dukes' stage of colorectal cancer[120,124] and proximity of T cells to the tumour[120] although there are clearly cancers in which this does not occur.[126] Stimulation with the proinflammatory cytokine IL-2 causes a significant increase in CD3-ζ chain-positive cells[123] but fails to increase tumour-specific cytolytic T-cell activity.[121] p561ck (lymphocyte cellular kinase) plays a key role in T-lymphocyte activation and differentiation. It is associated with a variety of cell surface receptors and is critical for signal transduction from the TCR.[127] Low levels have been detected in tumour infiltrating lymphocyte (TIL) of colorectal tumours[123] with increased expression found after exposure to IL-2.[128]

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