Pre-encoded responsiveness to type I interferon in the peripheral immune system defines outcome of PD1 blockade therapy View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-07-14

AUTHORS

Giselle M. Boukhaled, Ramy Gadalla, Heidi J. Elsaesser, Diala Abd-Rabbo, Rene Quevedo, S. Y. Cindy Yang, Mengdi Guo, Ben X. Wang, Babak Noamani, Diana Gray, Sally C. M. Lau, Kirsty Taylor, Kyaw Aung, Anna Spreafico, Aaron R. Hansen, Samuel D. Saibil, Naoto Hirano, Cynthia Guidos, Trevor J. Pugh, Tracy L. McGaha, Pamela S. Ohashi, Adrian G. Sacher, Marcus O. Butler, David G. Brooks

ABSTRACT

Type I interferons (IFN-Is) are central regulators of anti-tumor immunity and responses to immunotherapy, but they also drive the feedback inhibition underlying therapeutic resistance. In the present study, we developed a mass cytometry approach to quantify IFN-I-stimulated protein expression across immune cells and used multi-omics to uncover pre-therapy cellular states encoding responsiveness to inflammation. Analyzing peripheral blood cells from multiple cancer types revealed that differential responsiveness to IFN-Is before anti-programmed cell death protein 1 (PD1) treatment was highly predictive of long-term survival after therapy. Unexpectedly, IFN-I hyporesponsiveness efficiently predicted long-term survival, whereas high responsiveness to IFN-I was strongly associated with treatment failure and diminished survival time. Peripheral IFN-I responsive states were not associated with tumor inflammation, identifying a disconnect between systemic immune potential and ‘cold’ or ‘hot’ tumor states. Mechanistically, IFN-I responsiveness was epigenetically imprinted before therapy, poising cells for differential inflammatory responses and dysfunctional T cell effector programs. Thus, we identify physiological cell states with clinical importance that can predict success and long-term survival of PD1-blocking immunotherapy. More... »

PAGES

1273-1283

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41590-022-01262-7

    DOI

    http://dx.doi.org/10.1038/s41590-022-01262-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1149466583

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35835962


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