The importance of tumor microenvironment modulations in the progression of pancreatic intraductal papillary mucinous neoplasms†

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have attracted substantial attention since they represent the most prevalent macroscopic precursor of pancreatic cancer. Most lesions show an epithelium with low-grade dysplasia and will remain indolent and unknown to the patient. Notably, a subgroup of IPMNs will progress to invasive cancer through a stepwise process characterized by the accumulation of specific genomic alterations and concomitant modifications of the tumor microenvironment (TME). The manuscript of Jamouss et al, recently published in The Journal of Pathology, expands the current knowledge on TME dynamics in IPMNs. The neoplastic progression of IPMNs is paralleled by a shift toward an immunosuppressive TME, with depletion of cytotoxic T cells, elevated expression of immune checkpoint molecules, including PD-L1 and VISTA, and increased density of macrophages. Overall, TME modifications are crucial in the progression of pancreatic IPMNs, calling for potential therapeutic strategies focused on TME modulations for cancer interception. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.