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Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling

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机构： [1]Department of Neurosurgery, Pituitary Adenoma Multidisciplinary Center, West China Hospital of Sichuan University, Chengdu, China [2]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China [3]Department of Neurosurgery,Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China [4]Departments of Thoracic Oncology, West China Hospital of Sichuan University, Chengdu, Sichuan, China [5]Institute of Clinical Pathology, West China Hospital of SichuanUniversity, Chengdu, Sichuan, China [6]Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, China

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PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated.By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes.PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs.Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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大类 | 1 区

医学

小类 | 2 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

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出版当年[2023]版：

Q1 ONCOLOGY

最新[2023]版：

Q1 ONCOLOGY

影响因子： 6.4 最新[2023版] 8.1 最新五年平均 6.4 出版当年[2023版] 8.1 出版当年五年平均 8.8 出版前一年[2022版]

第一作者：

第一作者机构： [1]Department of Neurosurgery, Pituitary Adenoma Multidisciplinary Center, West China Hospital of Sichuan University, Chengdu, China [2]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China

通讯作者：

通讯机构： [2]State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, China [6]Department of Pathology, West China Second University Hospital, Sichuan University, Chengdu, China

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