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Single-cell transcriptomics reveal distinct immune-infiltrating phenotypes and macrophage-tumor interaction axes among different lineages of pituitary neuroendocrine tumors.
Lin, Shaojian; Dai, Yuting; Han, Changxi; Han, Tianyi; Zhao, Linfeng; Wu, Renyan; Liu, Jianyue; Zhang, Bo; Huang, Ning; Liu, Yanting; Lai, Shujing; Shi, Jintong; Wang, Yu; Lou, Meiqing; Xie, Jing; Cheng, Yijun; Tang, Hao; Yao, Hong; Fang, Hai; Zhang, Yan; Wu, Xuefeng; Shen, Lei; Ye, Youqiong; Xue, Li; Wu, Zhe Bao.
Afiliação
  • Lin S; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Dai Y; Department of Neurosurgery, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Han C; Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Han T; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhao L; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wu R; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Liu J; Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang B; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Huang N; Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Liu Y; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Lai S; Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Shi J; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wang Y; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Lou M; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xie J; Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Cheng Y; Department of Neurosurgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Tang H; Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Yao H; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Fang H; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang Y; Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wu X; Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Shen L; Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
  • Ye Y; Department of Neurosurgery, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Xue L; Shanghai Institute of Immunology, Department of Immunology and Microbiology and the Ministry of Education Key Laboratory of Cell Death and Differentiation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Wu ZB; Department of Neurosurgery, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. lshen@shsmu.edu.cn.
Genome Med ; 16(1): 60, 2024 04 24.
Article em En | MEDLINE | ID: mdl-38658971
ABSTRACT

BACKGROUND:

Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood.

METHODS:

The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis.

RESULTS:

The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis.

CONCLUSIONS:

In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Hipofisárias / Tumores Neuroendócrinos / Análise de Célula Única / Microambiente Tumoral / Transcriptoma / Macrófagos Limite: Animals / Humans Idioma: En Revista: Genome Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias Hipofisárias / Tumores Neuroendócrinos / Análise de Célula Única / Microambiente Tumoral / Transcriptoma / Macrófagos Limite: Animals / Humans Idioma: En Revista: Genome Med Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China