Recent advances in cancer immunotherapy have focused on manipulating co-signaling pathways to direct or fine-tune antitumor immune responses. This is based on the findings that co-signaling pathways are pivotal in positive and negative regulation of innate and adaptive immunity to antigens. Importantly, cancer cells as well as cells in cancer microenvironments often aberrantly express co-signaling molecules to evade tumor immunity. We will focus our discussion on two co-signaling pathways including CD137/CD137L and B7-H1/PD-1. The data from animal models and clinical trials indicate that monoclonal antibodies and recombinant proteins targeting these co-signaling molecules are able to stimulate antitumor immune responses or ablate immune suppression. Co-signaling molecules thus add a new modality for mechanism-based design of combined immunotherapy in the future.
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