@article {541966,
	title = {Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth.},
	journal = {Cell},
	volume = {162},
	number = {6},
	year = {2015},
	month = {2015 Sep 10},
	pages = {1242-56},
	abstract = {Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and~have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy.},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2015.08.052},
	author = {Kleffel, Sonja and Posch, Christian and Barthel, Steven R and Mueller, Hansgeorg and Schlapbach, Christoph and Guenova, Emmanuella and Elco, Christopher P and Lee, Nayoung and Juneja, Vikram R and Zhan, Qian and Lian, Christine G and Thomi, Rahel and Hoetzenecker, Wolfram and Cozzio, Antonio and Dummer, Reinhard and Mihm, Martin C and Flaherty, Keith T and Frank, Markus H and Murphy, George F and Sharpe, Arlene H and Kupper, Thomas S and Schatton, Tobias}
}
