Single cell RNA-Sequencing Reveals Mast Cells Enhance Mononuclear Phagocytes Infiltration in Bladder Cancer Microenvironment

  • J Cancer. 2024 Sep 3;15(17):5672-5690. doi: 10.7150/jca.99554.
Zige Liu  1  2 ,  Caisheng Huang  1  2  3 ,  Xingning Mao  2 ,  Junhao Mi  2 ,  Qingyun Zhang  2  4 ,  Yuli Xie  2  5 ,  Hao Yuan  2  5 ,  Mujia Jili  2  5 ,  Jiange Zhang  2  6 ,  Jianxin Chen  1  2  4 ,  Shengzhu Huang  2 ,  Zengnan Mo  1  2 ,  Rirong Yang  2  5
Affiliations
  • 1. Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, Guangxi, China.
  • 2. Center for Genomic and Personalized Medicine, Guangxi key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning 530021, Guangxi, China.
  • 3. Department of Urology, The Nanning Second People's Hospital, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
  • 4. Department of Urology, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
  • 5. Department of Immunology, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, Guangxi, China.
  • 6. Department of Urology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
PMID: 39308672 DOI: 10.7150/jca.99554
Abstract

Objective: Investigating the interaction between Mast cells (MCs) and Mononuclear Phagocytes (MPs) in the tumor microenvironment (TME) of blader Cancer (BCa) to uncover potential immunotherapeutic targets. Methods: Single-cell RNA Sequencing (scRNA-Seq) was conducted on 12 BCa patients to identify distinct subgroups of MCs and MPs. Transcriptome data was analyzed to characterize the phenotype, gene enrichment, cell-cell communication, and biological processes. The expression levels of cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), while the chemotactic effects of cytokines were evaluated through Transwell assay. Results: In muscle-invasive bladder Cancer (MIBC), the proportion of interferon-stimulated MC subtype (Mast-ISG15) increased. Mast-IL13 subgroup and Mast-CCL2 subgroups were functionally enriched in interferon (IFN) and nuclear factor kappa-B (NF-κB) signaling pathways. The Mast-CCL2 subgroup overexpressed the CCL2 gene, which could chemoattract MPs through CCL2. In vitro experiments confirmed that under stimulation, activated MCs activated IFN and NF-κB signaling, increasing the secretion of CCL2 and IL-13, chemoattracted THP-1 monocyte. Conclusion: This study revealed the vital role of MCs in shaping the TME of BCa. And provides new insights for the precise treatment of BCa.

Keywords
Blader Cancer; Mast Cell; Mononuclear Phagocytes; Single Cell RNA-Sequencing; Tumor Microenvironment.
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