Overcoming the Hurdles of Tumor Immunity by Targeting Regulatory Pathways in Innate and Adaptive Immune Cells

NORBERTO W. ZWIRNER; DIEGO O. CROCI; CAROLINA I. DOMAICA; GABRIEL A. RABINOVICH

Curr Pharm Des

Bentham Science Publishers

Lugar: Netherlands; Año: 2010 vol. 16 p. 255 - 267

1873-4286

Abstract: The improved understanding of the biochemical nature of tumor antigens and the identification of cellular and molecularmechanisms leading to activation of innate and adaptive immune cells have been of paramount importance in the progress of tumorimmunology. Studies on the intricate network of interactions between tumor and immune cells have revealed novel regulatory signals,including cell surface inhibitory receptors and costimulatory molecules, intracellular regulatory pathways, immunosuppressive cytokinesand proapoptotic mediators, which may operate in concert to orchestrate tumor-immune escape. This emerging portfolio of inhibitorycheckpoints can influence the physiology of innate immune cells including dendritic cells, macrophages and natural killer (NK) cells, aswell as different subsets of T cells to fine tune their effector function. The synergistic combination of strategies aimed at overcomingregulatory signals and/or stimulating effector pathways, may offer therapeutic advantage as adjuvants of conventional anticancertherapies. Based on this premise, we will discuss here how the control of the effector functions of innate and adaptive immune cells andthe manipulation of regulatory pathways, either alone or in combination, could be exploited for therapeutic purposes in cancer patients.