American Association for Cancer Research
21598290cd130458-sup-supp_table_1.xls (28 kB)

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

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posted on 2023-04-03, 20:46 authored by Tobias Bald, Jennifer Landsberg, Dorys Lopez-Ramos, Marcel Renn, Nicole Glodde, Philipp Jansen, Evelyn Gaffal, Julia Steitz, Rene Tolba, Ulrich Kalinke, Andreas Limmer, Göran Jönsson, Michael Hölzel, Thomas Tüting

XLS file 28K, List of top 50 interferon alpha induced gene across five humane melanoma cell lines



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