IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer.

Autor:	Heim L; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Yang Z; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Tausche P; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Hohenberger K; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Chiriac MT; Department of Internal Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Koelle J; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Geppert CI; Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Kachler K; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Miksch S; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Graser A; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Friedrich J; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Kharwadkar R; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States., Rieker RJ; Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Trufa DI; Department of Thoracic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Sirbu H; Department of Thoracic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Neurath MF; Department of Internal Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany., Kaplan MH; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States., Finotto S; Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Apr 20; Vol. 13, pp. 859738. Date of Electronic Publication: 2022 Apr 20 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.859738
Abstrakt:	Although lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment. Moreover, we noted IL-9 producing Tregs in NSCLC. IL-9 target cells in NSCLC consisted of IL-9R+ tumor cells and tumor-infiltrating lymphocytes. In two murine experimental models of NSCLC, and in vitro , IL-9 prevented cell death and controlled growth of lung adenocarcinoma cells. Targeted deletion of IL-9 resulted in successful lung tumor rejection in vivo associated with an induction of IL-21 and reduction of Treg cells. Finally, anti-IL-9 antibody immunotherapy resulted in suppression of tumor development even in established experimental NSCLC and was associated with reduced IL-10 production in the lung. In conclusion, our findings indicate that IL-9 drives immune escape of lung tumor cells via effects on tumor cell survival and tumor infiltrating T cells. Thus, strategies blocking IL-9 emerge as a new approach for clinical therapy of lung cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Heim, Yang, Tausche, Hohenberger, Chiriac, Koelle, Geppert, Kachler, Miksch, Graser, Friedrich, Kharwadkar, Rieker, Trufa, Sirbu, Neurath, Kaplan and Finotto.)
Databáze:	MEDLINE
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