胰管腺癌（PDAC）的特点是大量的脱细胞基质，由癌相关成纤维细胞（CAF）和交错的免疫细胞组成。非规范性CD8+ T细胞亚群产生IL-17A（Tc17）促进自身免疫，并在肿瘤中被识别。本文评估了Tc17在PDAC中的作用。Tc17细胞的浸润与患者总生存率和肿瘤分期相关。将野生型（WT）或Il17ra-/-休眠胰腺星形细胞（qPSC）暴露于Tc17细胞获得的条件性介质（Tc17-CM）中，并进行了Tc17-CM诱导的炎性（i）CAF（Tc17-iCAF）与肿瘤细胞的共培养。使用IL-17A / F，IL-17RA，RAG1缺陷和Foxn1nu / nu小鼠研究了Tc17在皮下和原位PDAC小鼠模型中的作用。在PDAC中，Tc17细胞的数量的增加高度相关于患者的生存率降低和肿瘤分期晚。Tc17-CM通过IL-17A和TNF的协同作用诱导iCAF差异化，通过iCAF关联基因的表达来评估。因此，IL-17RA控制了qPSC对Tc17-CM的响应。与Tc17-iCAF共培养的胰腺肿瘤细胞显示增强的增殖和参与增殖，新陈代谢和保护细胞凋亡的基因的表达。 Tc17-iCAF加速了Rag1- / -小鼠和Foxn1nu / nu小鼠中的小鼠和人类肿瘤的生长。最后，在体内需要由成纤维细胞表达的Il17ra来驱动Tc17的肿瘤生长。我们确定Tc17为PDAC中新的促进肿瘤发生的CD8+ T细胞亚型，它通过依赖于IL-17RA的基质修饰来加速肿瘤生长。我们描述了三种细胞类型之间的相互作用，Tc17，成纤维细胞和肿瘤细胞，促进PDAC的进展，并导致患者预后不良。 ©作者（或其雇主）2023。在CC BY-NC下允许重复使用。不进行商业重复使用。由BMJ出版。

Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8+ T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC.Infiltration of Tc17 cells in PDAC tissue was correlated with patient overall survival and tumour stage. Wild-type (WT) or Il17ra-/- quiescent pancreatic stellate cells (qPSC) were exposed to conditional media obtained from Tc17 cells (Tc17-CM); moreover, co-culture of Tc17-CM-induced inflammatory (i)CAF (Tc17-iCAF) with tumour cells was performed. IL-17A/F-, IL-17RA-, RAG1-deficient and Foxn1nu/nu mice were used to study the Tc17 role in subcutaneous and orthotopic PDAC mouse models.Increased abundance of Tc17 cells highly correlated with reduced survival and advanced tumour stage in PDAC. Tc17-CM induced iCAF differentiation as assessed by the expression of iCAF-associated genes via synergism of IL-17A and TNF. Accordingly, IL-17RA controlled the responsiveness of qPSC to Tc17-CM. Pancreatic tumour cells co-cultured with Tc17-iCAF displayed enhanced proliferation and increased expression of genes implicated in proliferation, metabolism and protection from apoptosis. Tc17-iCAF accelerated growth of mouse and human tumours in Rag1-/- and Foxn1nu/nu mice, respectively. Finally, Il17ra-expressed by fibroblasts was required for Tc17-driven tumour growth in vivo.We identified Tc17 as a novel protumourigenic CD8+ T-cell subtype in PDAC, which accelerated tumour growth via IL-17RA-dependent stroma modification. We described a crosstalk between three cell types, Tc17, fibroblasts and tumour cells, promoting PDAC progression, which resulted in poor prognosis for patients.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.