The interplay between natural killer cells and pancreatic stellate cells in pancreatic ductal adenocarcinoma

作者：Rachel Elizabeth Ann Fincham, Parthiban Periasamy, Craig Ryan Joseph, Jia Meng, Jeffrey Chun Tatt Lim, Felicia Wee, Konstantinos Stasinos, Michelle R. Goulart, Jiangfeng Ye, Li Yen Chong, Bijin Au, Denise Goh, Joe Yeong, Hemant M. Kocher · 发表于：癌症：英文版 · 年份：2024 · DOI：10.1002/cac2.12638 · 被引用次数：3 · 研究领域：Pancreatic and Hepatic Oncology Research、Phagocytosis and Immune Regulation、Cancer Cells and Metastasis

Pancreatic ductal adenocarcinoma (PDAC) remains one of medicine's most urgent areas of unmet need. With 5-year survival rates of ∼11%, PDAC is set to become the second leading cause of cancer related deaths by 2040 [1]. The complex tumour microenvironment (TME) in PDAC, responsible for poor prognosis, is comprised of extracellular matrix (ECM) proteins and multiple cell types; with pancreatic stellate cells (PSCs), which become activated cancer associated fibroblasts (CAFs), being regarded as key orchestrators of the TME. We have demonstrated that treatment with all-trans retinoic acid (ATRA) can render activated PSCs (aPSC) to a quiescent (qPSC) phenotype (shift to G1 phase of cell cycle and other features [2]), resulting in stromal remodelling and thus, influencing cancer cell co-targeting with chemotherapy in patients [3]. This has resulted in the use of ATRA along with standard-of-care chemotherapy in the Stromal TARgeting for PAncreatic Cancer (STARPAC) clinical trial, with promising results [4]. These clinically relevant [5], exciting potential therapeutic benefits of stromal co-targeting through rendering PSCs quiescent [6], along with predictive inflammation-related biomarkers [7], and increased focus on cellular therapeutics such as NK cells, led us to postulate potential targetable PSC-immune cell interactions which may uncover a comprehensive therapeutic strategy for treating hitherto, incurable PDAC. We identified differential NK-92 (a cell line representing NK ce...