Durable antitumor responses to CD47 blockade require adaptive immune stimulation Article Swipe
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· 2016
· Open Access
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· DOI: https://doi.org/10.1073/pnas.1604268113
· OA: W2339658610
Significance Therapeutic antitumor antibodies are widely used clinically. CD47 is an antiphagocytic ligand expressed by tumors that binds the inhibitory receptor signal regulatory protein alpha (SIRPα) on phagocytic cells. Interruption of CD47–SIRPα interactions in immunodeficient mice bearing human tumors enhances therapeutic antitumor antibody responses by promoting phagocytosis of antibody-bound tumor cells. Here, we use a novel anti-CD47 single domain antibody, derived from an alpaca, in an immunocompetent mouse model of melanoma and find that, in contrast to immunodeficient models, CD47 blockade alone is insufficient to enhance the effects of antimelanoma antibodies. However, when combined with blockade of programmed death-ligand 1 (PD-L1), an immune receptor that inhibits antitumor T cell responses, we find synergistic activity, suggesting a role for both innate and adaptive inhibitory pathways in the response to therapeutic antibodies.
