SMS2 siRNA inhibits pancreatic tumor growth by tumor microenvironment modulation.

The massive infiltration of suppressor immune cells within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) is a major cause of treatment resistance. Reducing this infiltration may represent a potentially effective therapeutic strategy. Sphingomyelin synthase 2 (SMS2) is a crucial enzyme for sphingomyelin synthesis, contributing significantly to the integrity and function of the plasma membrane. In this study, we developed a self-assembling SMS2 siRNA gene expression plasmid for in vivo delivery. The SMS2 siRNA specifically inhibits SMS2 expression while preserving the expression and activity of SMS1. Administration of the self-assembling SMS2 siRNA suppresses tumor growth in a murine model of Panc02 pancreatic carcinoma, modulates the polarization of tumor-associated macrophages (TAMs), and reduces the infiltration of tumor-associated neutrophils (TANs) by regulating the NF-κB/CXCL5 pathway. Consequently, utilizing SMS2 siRNA to improve the local immunosuppressive microenvironment holds promise for pancreatic cancer therapy. Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Xin Jiang, Ziqing Yuan, Tingbo Ding, Ker Yu, Jibin Dong. SMS2 siRNA inhibits pancreatic tumor growth by tumor microenvironment modulation. International immunopharmacology. 2024 Dec 05;142(Pt A):113111

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PMID: 39255679

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