IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer

Tertiary lymphoid structures (TLSs) are de novo ectopic lymphoid aggregates that regulate immunity in chronically inflamed tissues, including tumours. Although TLSs form due to inflammation-triggered activation of the lymphotoxin (LT)–LTβ receptor (LTβR) pathway1, the inflammatory signals and cells that induce TLSs remain incompletely identified. Here we show that interleukin-33 (IL-33), the alarmin released by inflamed tissues2, induces TLSs. In mice, Il33 deficiency severely attenuates inflammation- and LTβR-activation-induced TLSs in models of colitis and pancreatic ductal adenocarcinoma (PDAC). In PDAC, the alarmin domain of IL-33 activates group 2 innate lymphoid cells (ILC2s) expressing LT that engage…

• BS
  Bristol-Myers Squibb
• MS
  Memorial Sloan-Kettering Cancer Center

  Award: P30 CA08748
• CA
  Crohn's and Colitis Foundation

  Award: 937437
• PS
  Pershing Square Sohn Cancer Research Alliance
• CF
  Cycle for Survival
• NI
  National Institutes of Health

  Awards: P30 CA08748, CA08748
• WC
  Weill Cornell Medical College
• MA
  Marie-Josée and Henry R. Kravis Center for Molecular Oncology
• NC
  National Cancer Institute

  Awards: P30 CA08748, CA08748