Immunotherapy and immunoescape in colorectal cancer

GUILLERMO MAZZOLINI, OIHANA MURILLO, CATALINA ATORRASAGASTI, JUAN DUBROT, IñIGO TIRAPU,

WORLD JOURNAL OF GASTROENTEROLOGY

The WJG Press

Lugar: Beijing ; Año: 2007 vol. 28 p. 5822 - 5831

1007-9327

Immunotherapy encompasses a variety of interventionsand techniques with the common goal of elicitingtumor cell destructive immune responses. Colorectalcarcinoma often presents as metastatic disease thatimpedes curative surgery. Novel strategies such asactive immunization with dendritic cells (DCs), genetransfer of cytokines into tumor cells or administration ofimmunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinicalstudies and are at an early clinical development stage.Importantly, there is accumulating evidence thatchemotherapy and immunotherapy can be combinedin the treatment of some cases with colorectal cancer,with synergistic potentiation as a result of antigenscross-presented by dendritic cells and/or eliminationof competitor or suppressive T lymphocyte populations(regulatory T-cells). However, genetic and epigeneticunstable carcinoma cells frequently evolve mechanismsof immunoevasion that are the result of either lossof antigen presentation, or an active expression ofimmunosuppressive substances. Some of these activelyimmunosuppressive mechanisms are inducible bycytokines that signify the arrival of an effector immuneresponse. For example, induction of 2, 3 indoleaminedioxygenase (IDO) by IFNã in colorectal carcinoma cells.Combinational and balanced strategies fostering antigenpresentation, T-cell costimulation and interference withimmune regulatory mechanisms will probably takethe stage in translational research in the treatment ofcolorectal carcinoma.