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immunotherapy and immunoescape in colorectal cancer

World Journal of Gastroenterology 2007年第44期13卷 5822-5831页

作者： Guillermo Mazzolini Oihana Murillo Catalina Atorrasagasti Juan Dubrot iigo tirapu Miguel Rizzo Ainhoa Arina Carlos Alfaro Arantza Azpilicueta Carmen Berasain José L Perez-Gracia Alvaro Gonzalez ignacio Melero Liver Unit Facultad de Ciencias Biomédicas Universidad Austral Presidente Perón 1500 (1635) Derqui-Pilar Buenos Aires Argentina Centro de investigación Médica Aplicada and Clínica Universitaria Universidad de Navarra Pamplona Spain

immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (iDO) by iFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma.

关键词： Colorectal carcinoma immunotherapy Gene therapy interleukin-12 Dendritic cells CD137 indoleamine 2, 3 dioxygenase

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