Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy
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s41467-021-26407-4.pdf
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Published version
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823.53 KB
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Author(s)
Bent, Eric H
Millán-Barea, Luis R
Zhuang, Iris
Goulet, Daniel R
Fröse, Julia
Hemann, Michael T
Date Issued
2021
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Bent, Eric H, Millán-Barea, Luis R, Zhuang, Iris, Goulet, Daniel R, Fröse, Julia et al. 2021. "Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy." Nature Communications, 12 (1).
Version
Final published version
Abstract
Cytotoxic chemotherapeutics primarily function through DNA damage-induced tumor cell apoptosis, although the inflammation provoked by these agents can stimulate anti-cancer immune responses. The mechanisms that control these distinct effects and limit immunogenic responses to DNA-damage mediated cell death in vivo are currently unclear. Using a mouse model of BCR-ABL+ B-cell acute lymphoblastic leukemia, we show that chemotherapy-induced anti-cancer immunity is suppressed by the tumor microenvironment through production of the cytokine IL-6. The chemotherapeutic doxorubicin is curative in IL-6-deficient mice through the induction of CD8+ T-cell-mediated anti-cancer responses, while moderately extending lifespan in wild type tumor-bearing mice. We also show that IL-6 suppresses the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. Our results suggest that IL-6 is a key regulator of anti-cancer immune responses induced by genotoxic stress and that its inhibition can switch cancer cell clearance from primarily apoptotic to immunogenic, promoting and maintaining durable anti-tumor immune responses.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-021-26407-4
