Immune Suppression and Colorectal Cancer

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

Disclosures

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

In This Article

VEGF

Vascular endothelial growth factor is secreted by many tumours[175] including colorectal carcinomas.[176,177] VEGF is the predominant angiogenic factor in human colorectal cancer,[178] being associated with tumour cell proliferation,[176] the stage of the disease[179] including the development of metastasis[180] and poor prognosis.[178] VEGF is not only important for tumour vascularization, but also induces immune suppression.[181]

Evidence for this comes from work demonstrating that VEGF inhibits both DC maturation[182,183] and function.[184] It induces DC apoptosis and alters DC immunophenotypic profile.[116] VEGF interferes with the development of T cells from early haematopoietic progenitor cells,[185] correlates with reduced levels of the antitumour cytokine IL-12[181] and is associated with an increase in the production of immature myeloid cells.[182]

Bevacizumab is a humanized monoclonal antibody that inhibits VEGF. In combination with chemotherapy it can now be used as a first-line therapy for the treatment of patients with metastatic colorectal cancer[186] as it improves survival.[187] Its antitumour activity is most likely because of its antiangiogenesis effect;[188] however, exposure to anti-VEGF blocking antibodies reverses the inhibitory effect on DC improving both their function and numbers.[116,182]

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