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.
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.
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.
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.