 IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancerNicoletta Caronni (),
Federica La Terza,
Francesco M. Vittoria,
Giulia Barbiera,
Luca Mezzanzanica,
Vincenzo Cuzzola,
Simona Barresi,
Marta Pellegatta,
Paolo Canevazzi,
Garett Dunsmore,
Carlo Leonardi,
Elisa Montaldo,
Eleonora Lusito,
Erica Dugnani,
Antonio Citro,
Melissa S. F. Ng,
Marco Schiavo Lena,
Denise Drago,
Annapaola Andolfo,
Silvia Brugiapaglia,
Alessandro Scagliotti,
Alessandra Mortellaro,
Vincenzo Corbo,
Zhaoyuan Liu,
Anna Mondino,
Paolo Dellabona,
Lorenzo Piemonti,
Carla Taveggia,
Claudio Doglioni,
Paola Cappello,
Francesco Novelli,
Matteo Iannacone,
Lai Guan Ng,
Florent Ginhoux,
Stefano Crippa,
Massimo Falconi,
Chiara Bonini,
Luigi Naldini,
Marco Genua and
Renato Ostuni ()
Nature, 2023, vol. 623, issue 7986, 415-422 Abstract: Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with high resistance to therapies1. Inflammatory and immunomodulatory signals co-exist in the pancreatic tumour microenvironment, leading to dysregulated repair and cytotoxic responses. Tumour-associated macrophages (TAMs) have key roles in PDAC2, but their diversity has prevented therapeutic exploitation. Here we combined single-cell and spatial genomics with functional experiments to unravel macrophage functions in pancreatic cancer. We uncovered an inflammatory loop between tumour cells and interleukin-1β (IL-1β)-expressing TAMs, a subset of macrophages elicited by a local synergy between prostaglandin E2 (PGE2) and tumour necrosis factor (TNF). Physical proximity with IL-1β+ TAMs was associated with inflammatory reprogramming and acquisition of pathogenic properties by a subset of PDAC cells. This occurrence was an early event in pancreatic tumorigenesis and led to persistent transcriptional changes associated with disease progression and poor outcomes for patients. Blocking PGE2 or IL-1β activity elicited TAM reprogramming and antagonized tumour cell-intrinsic and -extrinsic inflammation, leading to PDAC control in vivo. Targeting the PGE2–IL-1β axis may enable preventive or therapeutic strategies for reprogramming of immune dynamics in pancreatic cancer. Date: 2023 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:623:y:2023:i:7986:d:10.1038_s41586-023-06685-2 Ordering information: This journal article can be ordered from DOI: 10.1038/s41586-023-06685-2 Access Statistics for this article Nature is currently edited by Magdalena Skipper More articles in Nature from Nature |
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