The immunology of colorectal cancer.
Despite the fact that the vast majority of differentiated colorectal cancers express tumour-associated antigens (TAA's) such as Carcinoembryonic antigen (CEA) and Ep-CAM, the immune response particularly in advanced disease is often attenuated. This may result from clonal immunocyte energy to oncofetal antigens normally expressed during cell development, immune complex disease where the TAA is repeatedly shed into the circulation and tumour-induced impairments in T cell receptor recognition and stimulation. Commonly used monoclonal anti-TAA antibody therapy is also hampered by human anti-xenogeneic antibody production and by the physical distribution of the antibody into the center of tumour deposits where blood flow is limited and where tumour neovasculature is hyperpermeable. Moreover, animal models of colorectal cancer should be assessed carefully since CEA is not normally expressed, requiring the transduction of CEA cDNA into tumour xenografts or the creation of transgenic species where the mechanisms of tumour rejection are still governed by non-human antigenic histoincompatibility. All of this has resulted in the generation of novel immune constructs designed to enhance the inherent immunogenicity of colorectal cancer, using antigenic viral genomes or cytokine transduction methodology as well as the ex vivo stimulation of dendritic antigen-presenting cells or autologous tumour-infiltrating lymphocytes. Even these powerful strategies may be foiled by intratumoural mechanisms which result in excessive apoptosis of infused cells even when they have been shown in vitro to be immunocompetent and tumour-specific. This review discusses these immune approaches in colorectal cancer and their inherent limitations.
Zbar
A P
AP
University of the West Indies, Cave Hill Campus, Queen Elizabeth Hospital, St. Michael, Barbados. azbar@uwichill.edu.bb
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007108:Immune Tolerance; D007167:Immunotherapy
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen