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Cited by 256

The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.

Immune Cell–Poor Melanomas Benefit from PD-1 Blockade after Targeted Type I IFN Activation

Bald, Tobias, Landsberg, Jennifer, Lopez-Ramos, Dorys, Renn, Marcel, Glodde, Nicole, Jansen, Philipp, Gaffal, Evelyn, Steitz, Julia, Tolba, Rene, Kalinke, Ulrich, Limmer, Andreas, Jönsson, Göran, Hölzel, Michael, Tüting, Thomas·2014·Cancer Discovery
DOI 10.1158/2159-8290.cd-13-0458
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Abstract

Infiltration of human melanomas with cytotoxic immune cells correlates with spontaneous type I IFN activation and a favorable prognosis. Therapeutic blockade of immune-inhibitory receptors in patients with preexisting lymphocytic infiltrates prolongs survival, but new complementary strategies are needed to activate cellular antitumor immunity in immune cell–poor melanomas. Here, we show that primary melanomas in Hgf-Cdk4R24C mice, which imitate human immune cell–poor melanomas with a poor outcome, escape IFN-induced immune surveillance and editing. Peritumoral injections of immunostimulatory RNA initiated a cytotoxic inflammatory response in the tumor microenvironment and significantly impaired tumor growth. This critically required the coordinated induction of type I IFN responses by dendritic, myeloid, natural killer, and T cells. Importantly, antibody-mediated blockade of the IFN-induced immune-inhibitory interaction between PD-L1 and PD-1 receptors further prolonged the survival. These results highlight important interconnections between type I IFNs and immune-inhibitory receptors in melanoma pathogenesis, which serve as targets for combination immunotherapies. Significance: Using a genetically engineered mouse melanoma model, we demonstrate that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune-inhibitory receptors is a rational strategy to expose immune cell–poor tumors to cellular immune surveillance. Cancer Discov; 4(6); 674–87. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 621

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Metadata

Authors
Bald, T., Landsberg, J., Lopez-Ramos, D., Renn, M., Glodde, N., Jansen, P., Gaffal, E., Steitz, J., Tolba, R., Kalinke, U., Limmer, A., Jönsson, G., Hölzel, M., & Tüting, T.
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2014-06-01
Volume
4
Issue
6
Pages
674-687
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-13-0458
OpenAlex
W2147598914
Cited by
256
References
48
FWCI
12.21
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Immune Cell–Poor Melanomas Benefit from PD-1 Blockade after Targeted Type I IFN Activation. https://app.cochat.ai/papers/10.1158/2159-8290.cd-13-0458
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Bald, T., Landsberg, J., Lopez-Ramos, D., Renn, M., Glodde, N., Jansen, P., Gaffal, E., Steitz, J., Tolba, R., Kalinke, U., Limmer, A., Jönsson, G., Hölzel, M., & Tüting, T. (2014). Immune Cell–Poor Melanomas Benefit from PD-1 Blockade after Targeted Type I IFN Activation. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-13-0458

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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.