Research ArticleCancer

In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy

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Science Translational Medicine  10 May 2017:
Vol. 9, Issue 389, eaal3604
DOI: 10.1126/scitranslmed.aal3604

Tug-of-war with anti–PD-1

Antibodies against immune checkpoints such as programmed death–1 (PD-1) are gaining increasing prominence in cancer treatment, but even these promising therapeutics do not always work. To be effective in preventing T cells from becoming exhausted, anti–PD-1 antibodies must be able to remain bound to the T cells. Unfortunately, this does not always happen, as Arlauckas et al. discovered. Although anti–PD-1 antibodies initially bound to T cells as intended, the authors found that tumor-associated macrophages quickly removed these antibodies from T cells, thus inactivating them. The researchers also identified a potential way to overcome this problem, showing that inhibition of Fcγ receptors prevented removal of anti–PD-1 and prolonged its effects in vivo.