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  3. Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression

Single-cell and spatial transcriptome analyses reveal tumor heterogeneity and immune remodeling involved in pituitary neuroendocrine tumor progression

  • Nat Commun. 2025 May 30;16(1):5007. doi: 10.1038/s41467-025-60028-5.
Wan Su # 1,  Zhang Ye # 2,  Jifang Liu # 2,  Kan Deng 2,  Jinghua Liu 1,  Huijuan Zhu 1,  Lian Duan 1,  Chen Shi 1,  Linjie Wang 1,  Yuxing Zhao 1,  Fengying Gong 1,  Yi Zhang 2,  Bo Hou 3,  Hui You 3,  Feng Feng 3,  Qing Ling 4,  Yu Xiao 4,  Yongdong Guo 5,  Wenyi Fan 6 7,  Sumei Zhang 8,  Zixin Zhang 8,  Xiaomin Hu 9,  Yong Yao 10,  Chunhong Zheng 11 12,  Lin Lu 13
Affiliations

Affiliations

  • 1 Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 2 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 3 Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 4 Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
  • 6 State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumor, Peking University Cancer Hospital & Institute, Beijing, China.
  • 7 Frontiers Science Center for Cancer Integrative Omics, Peking University International Cancer Institute, Peking University, Beijing, China.
  • 8 Clinical Biobank, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 9 State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. huxiaomin@pumch.cn.
  • 10 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. yaoyong@pumch.cn.
  • 11 State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumor, Peking University Cancer Hospital & Institute, Beijing, China. chunhong_zheng@bjmu.edu.cn.
  • 12 Frontiers Science Center for Cancer Integrative Omics, Peking University International Cancer Institute, Peking University, Beijing, China. chunhong_zheng@bjmu.edu.cn.
  • 13 Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. lulin@pumch.cn.
  • # Contributed equally.
PMID: 40442104 DOI: 10.1038/s41467-025-60028-5
Abstract

Pituitary neuroendocrine tumors (PitNETs) can be invasive or aggressive, yet the mechanisms behind these behaviors remain poorly understood, impeding treatment advancements. Here, we integrat single-cell RNA Sequencing and spatial transcriptomics, analyzing over 177,000 cells and 35,000 spots across 57 tissue samples. This comprehensive approach facilitates the identification of PitNETs tumor populations and characterizes the reconfiguration of the tumor microenvironment (TME) as PitNETs progress and invade. We trace the trajectory of TPIT-lineage PitNETs and identify an aggressive tumor cluster marked by elevated p53-mediated proliferation and a higher Trouillas classification, both associated with tumor progression. Additionally, we document the heterogeneity of immune stromal cells within PitNETs, particularly noting the enrichment of SPP1+ tumor associated macrophages (TAMs) in invasive tumors. These TAMs facilitate tumor invasion through the SPP1-ITGAV/ITGB1 signaling pathway. Our in-depth single-cell and spatial analysis of PitNETs uncovers the molecular dynamics within the TME, suggesting potential targets for therapeutic intervention.

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