ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity Journal Article


Authors: Moral, J. A.; Leung, J.; Rojas, L. A.; Ruan, J.; Zhao, J.; Sethna, Z.; Ramnarain, A.; Gasmi, B.; Gururajan, M.; Redmond, D.; Askan, G.; Bhanot, U.; Elyada, E.; Park, Y.; Tuveson, D. A.; Gönen, M.; Leach, S. D.; Wolchok, J. D.; DeMatteo, R. P.; Merghoub, T.; Balachandran, V. P.
Article Title: ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity
Abstract: Group 2 innate lymphoid cells (ILC2s) regulate inflammation and immunity in mammalian tissues1,2. Although ILC2s are found in cancers of these tissues3, their roles in cancer immunity and immunotherapy are unclear. Here we show that ILC2s infiltrate pancreatic ductal adenocarcinomas (PDACs) to activate tissue-specific tumour immunity. Interleukin-33 (IL33) activates tumour ILC2s (TILC2s) and CD8+ T cells in orthotopic pancreatic tumours but not heterotopic skin tumours in mice to restrict pancreas-specific tumour growth. Resting and activated TILC2s express the inhibitory checkpoint receptor PD-1. Antibody-mediated PD-1 blockade relieves ILC2 cell-intrinsic PD-1 inhibition to expand TILC2s, augment anti-tumour immunity, and enhance tumour control, identifying activated TILC2s as targets of anti-PD-1 immunotherapy. Finally, both PD-1+ TILC2s and PD-1+ T cells are present in most human PDACs. Our results identify ILC2s as anti-cancer immune cells for PDAC immunotherapy. More broadly, ILC2s emerge as tissue-specific enhancers of cancer immunity that amplify the efficacy of anti-PD-1 immunotherapy. As ILC2s and T cells co-exist in human cancers and share stimulatory and inhibitory pathways, immunotherapeutic strategies to collectively target anti-cancer ILC2s and T cells may be broadly applicable. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Keywords: adult; controlled study; human tissue; aged; human cell; cancer growth; nonhuman; pancreas; cd8+ t lymphocyte; animal cell; mouse; mammalia; mus; cell function; cancer immunotherapy; immune system; animal experiment; animal model; protein; skin; skin tumor; cancer infiltration; pancreas adenocarcinoma; tumor immunity; immunity; tumor; immunocompetent cell; tissue specificity; programmed death 1 receptor; lymphoid cell; interleukin 33; cancer; human; male; female; priority journal; article
Journal Title: Nature
Volume: 579
Issue: 7797
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2020-03-05
Start Page: 130
End Page: 135
Language: English
DOI: 10.1038/s41586-020-2015-4
PUBMED: 32076273
PROVIDER: scopus
PMCID: PMC7060130
DOI/URL:
Notes: Article -- Export Date: 1 April 2020 -- Source: Scopus
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  1. Jedd D Wolchok
    905 Wolchok
  2. Taha Merghoub
    364 Merghoub
  3. Mithat Gonen
    1029 Gonen
  4. Umeshkumar Kapaldev Bhanot
    93 Bhanot
  5. Billel Gasmi
    18 Gasmi
  6. Gokce Askan
    77 Askan
  7. John Alec Gaite Moral
    8 Moral
  8. Jennifer Jin Ruan
    4 Ruan
  9. Pui Ting J Leung
    5 Leung
  10. Zachary Michael Sethna
    15 Sethna