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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1525083
This article is part of the Research Topic STING Signaling in Cancer Immunotherapy View all 3 articles

IFNλ1 is a STING-dependent mediator of DNA damage and induces Immune activation in lung cancer

Provisionally accepted
Stine H Godsk Stine H Godsk 1Caroline MS Jensen Caroline MS Jensen 1Trine V Larsen Trine V Larsen 1Johanne Ahrenfeldt Johanne Ahrenfeldt 2,3Kristine R Gammelgaard Kristine R Gammelgaard 1Martin R Jakobsen Martin R Jakobsen 1*
  • 1 Aarhus University, Aarhus, Denmark
  • 2 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
  • 3 Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Capital Region of Denmark, Denmark

The final, formatted version of the article will be published soon.

    The importance of the cGAS-STING pathway and type I interferon (IFN) in anti-tumor immunity has been widely studied. However, we have limited knowledge about the role of type III IFNs in cancer. Type III IFNs, comprising IFNλ1-4, are opposite to type I IFN only expressed by a few cell types, including epithelial cells. The expression of one subunit of the type III IFN receptor, IFNLR1, is equally expressed only on a limited type of cells, which include epithelial cells. We found that nonsmall cell lung cancer (NSCLC) cell lines secreted IFNλ following STING activation whereas only few of these cell lines expressed IFNβ, and treatment with chemotherapy preferentially induce IFNλ. We observed that expression of IFNLR1 was downregulated in cancer cells, but by rescuing IFNLR1 expression, NSCLC cell lines became sensitized to an IFNλ-response leading to reduction in cell viability. Our findings suggest that downregulation of IFNLR1 can be a cancer immune evasion mechanism, and rescuing IFNLR1 expression in NSCLC in conjunction to chemotherapy could elevate anti-tumoral responses.Another reference suggested by Reviewer 2 has been added.

    Keywords: cancer immunology, STING, interferon lambda, NSCLC, CRISPR/Cas9

    Received: 08 Nov 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Godsk, Jensen, Larsen, Ahrenfeldt, Gammelgaard and Jakobsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Martin R Jakobsen, Aarhus University, Aarhus, Denmark

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.