title: Immunotherapy and immunoescape in colorectal cancer.
abstract: 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 IFNgamma 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.
authors.affiliation: Liver Unit, Facutad de Ciencias Biomédicas, Universidad Austral, Av Presidente Péron 1500, (1635) Derqui-Pilar, Buenos Aires, Argentina. gmazzoli@cas.austral.edu.ar
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Oihana
authors.initials: O
authors.lastname: Murillo
authors.forename: Catalina
authors.initials: C
authors.lastname: Atorrasagasti
authors.forename: Juan
authors.initials: J
authors.lastname: Dubrot
authors.forename: Iñigo
authors.initials: I
authors.lastname: Tirapu
authors.forename: Miguel
authors.initials: M
authors.lastname: Rizzo
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Arina
authors.forename: Carlos
authors.initials: C
authors.lastname: Alfaro
authors.forename: Arantza
authors.initials: A
authors.lastname: Azpilicueta
authors.forename: Carmen
authors.initials: C
authors.lastname: Berasain
authors.forename: José L
authors.initials: JL
authors.lastname: Perez-Gracia
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D007114:Immunization; D007167:Immunotherapy / Q000379:methods*; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal