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Cited by 639

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth

Open access
Kleffel, Sonja, Posch, Christian, Barthel, Steven R., Mueller, Hansgeorg, Schlapbach, Christoph, Guenova, Emmanuella, Elco, Christopher P., Lee, Nayoung, Juneja, Vikram R., Zhan, Qian, Lian, Christine G., Thomi, Rahel, Hoetzenecker, Wolfram, Cozzio, Antonio, Dummer, Reinhard, Mihm, Martin C., Flaherty, Keith T., Frank, Markus H., Murphy, George F., Sharpe, Arlene H., Kupper, Thomas S., Schatton, Tobias·2015·Cell
DOI 10.1016/j.cell.2015.08.052
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Abstract

SUMMARY 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 RNA interference, 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.

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Metadata

Authors
Kleffel, S., Posch, C., Barthel, S. R., Mueller, H., Schlapbach, C., Guenova, E., Elco, C. P., Lee, N., Juneja, V. R., Zhan, Q., Lian, C. G., Thomi, R., Hoetzenecker, W., Cozzio, A., Dummer, R., Mihm, M. C., Flaherty, K. T., Frank, M. H., Murphy, G. F., Sharpe, A. H., Kupper, T. S., & Schatton, T.
Venue
Cell
Publisher
Elsevier BV
Published
2015-09
Volume
162
Issue
6
Pages
1242-1256
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2015.08.052
OpenAlex
W2146774792
Cited by
639
References
33
FWCI
21.19
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. https://app.cochat.ai/papers/10.1016/j.cell.2015.08.052
The paper
Kleffel, S., Posch, C., Barthel, S. R., Mueller, H., Schlapbach, C., Guenova, E., Elco, C. P., Lee, N., Juneja, V. R., Zhan, Q., Lian, C. G., Thomi, R., Hoetzenecker, W., Cozzio, A., Dummer, R., Mihm, M. C., Flaherty, K. T., Frank, M. H., Murphy, G. F., . . . Schatton, T. (2015). Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth. Cell. https://doi.org/10.1016/j.cell.2015.08.052

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.