IL-33 and ILC2s Drive Immune Structures to Combat Pancreatic Cancer

A recent study published in Nature identifies interleukin-33 (IL-33) and group 2 innate lymphoid cells (ILC2s) as critical players in forming tertiary lymphoid structures (TLSs) within pancreatic ductal adenocarcinoma (PDAC), revealing a potential target for immunotherapy. The researchers discovered that IL-33, released by inflamed tissues, activates ILC2s to initiate TLS formation through lymphotoxin signaling, significantly enhancing immune responses in tumor environments. Importantly, these ILC2s migrate from the gut to pancreatic tumors, influenced by the gut microbiome. Human PDAC samples containing these TLSs correlated with improved patient prognosis. Leveraging these insights, researchers engineered a recombinant IL-33 protein that significantly expanded intratumoral ILC2s and TLSs in mouse models, demonstrating potent anti-tumor effects and highlighting a promising immunotherapeutic strategy against pancreatic cancer.