Work

SMS2 siRNA inhibits pancreatic tumor growth by tumor microenvironment modulation

Year: 2024

Type: article

Abstract: • Self-assembled siRNA plasmid with excellent SMS2 specificity and therapeutic effect on pancreatic cancer. • Inhibition of SMS2 reduces Suppressive immune cells infiltration in the tumor microenvironment. • SMS2 affects neutrophil recruitment to the TME and influences TAM polarisation by regulating NF-κB/CXCL5. • Inhibition of SMS2 activates anti-tumor immunity in T cells. 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.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2024.113111

Authors: Xin Jiang, Ziqing Yuan, Tingbo Ding, Ker Yu, Jibin Dong

Institution: Fudan University

Language: English

Topic: Pancreatic and Hepatic Oncology Research

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,250