Translational Therapeutics

Interleukin-10-regulated tumour tolerance in non-small cell lung cancer

  • British Journal of Cancer volume 117, pages 16441655 (21 November 2017)
  • doi:10.1038/bjc.2017.336
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Abstract

Background:

Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape.

Methods:

Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer.

Results:

Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide. IL-10 and IL-10R were found induced in cells surrounding the lung tumour cells, and IL-10R was mainly expressed on the surface of Foxp-3+ T-regulatory lymphocytes infiltrating the tumour of these patients where its expression inversely correlated with programmed cell death 1. These findings were confirmed in translational studies. In a human lung adenocarcinoma cell line, IL-10R was found induced under metabolic restrictions present during tumour growth, whereby IL-10 inhibited PDL1 and tumour cell apoptosis.

Conclusions:

These new findings suggest that IL-10 counteracts IFN-γ effects on PD1/PDL1 pathway, resulting in possible resistance of the tumour to anti-PD1/PDL1 immunotherapy.

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Change history

  • Corrected online 21 November 2017

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Acknowledgements

We thank Bettina Klösch, Corinna Holzinger and Rebekka Springel for their excellent experimental help. This work was financially supported by an IZKF grant number A59 in Erlangen awarded to SF. JMV was supported by a fellowship on Cellular Immune-intervention in Erlangen, sponsored by the graduated school of the SFB-643 group in Erlangen. We thank the all supporting team in the Molecular Pneumology department, Thoracic Surgery and Institute of Pathology in Erlangen.

Author contributions

JMV did the histological and immune-histological analysis including correlations, did the A549 experiments and wrote the manuscript, and generated the figures. JF helped with the generation of the figures and with the patients sample collection. LB did the real-time PCR for IL-10 and IL-10R in patients. DIT and HS provided and indexing the human lung biopsies. RR, CG and NF did the pathological characterization and digitalisation of the human tissue arrays originated from those biopsies, as well as the quality control of slides, stains and scans. SM did the immunohistochemical staining. LH and KK contributed to the patient samples collection and did the FACS analysis on human and in murine lung cells. LH and NS supported JMV and ST in the planning and executing numerous experiments related to the cell line A549. SF designed and supervised this study, and contributed significantly to the manuscript and figures.

Author information

Author notes

    • Julius Malte Vahl

    The present work was performed in fulfilment of the requirements for obtaining the degree ‘Dr med’ for Julius Vahl.

Affiliations

  1. Laboratory of Cellular and Molecular Lung Immunology, Department of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Hartmannstraβe 14, Erlangen 91052, Germany

    • Julius Malte Vahl
    • , Juliane Friedrich
    • , Susanne Mittler
    • , Sonja Trump
    • , Lisanne Heim
    • , Katerina Kachler
    • , Liubov Balabko
    • , Nina Sopel
    •  & Susetta Finotto
  2. Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Krankenhausstraβe 8-10, Erlangen 91054, Germany

    • Nicole Fuhrich
    • , Carol-Immanuel Geppert
    •  & Ralf Rieker
  3. Department of Thoracic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Krankenhausstraβe 12, Erlangen 91054, Germany

    • Denis Iulian Trufa
    •  & Horia Sirbu

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to Susetta Finotto.

Supplementary information

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Creative Commons BY-NC-SAFrom twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/