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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1494025
This article is part of the Research Topic Biomarker Discovery and Therapeutic Innovations in Genito-Urinary Cancer Management View all 7 articles

Single-cell transcriptomics reveals the heterogeneity and function of mast cells in human ccRCC

Provisionally accepted
Xiyu Song Xiyu Song 1,2*Jianhua Jiao Jianhua Jiao 3*
  • 1 Air Force Medical University, Xi'an, China
  • 2 National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi’an, China
  • 3 Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China

The final, formatted version of the article will be published soon.

    The role of mast cells (MCs) in clear cell renal carcinoma (ccRCC) is unclear, and comprehensive single-cell studies of ccRCC MCs have not yet been performed. To investigate the heterogeneity and effects of MCs in ccRCC, we studied single-cell transcriptomes from four ccRCC patients, integrating both single-cell sequencing and bulk tissue sequencing data from online sequencing databases, followed by validation via spatial transcriptomics and multiplex immunohistochemistry (mIHC). We identified four MC signature genes (TPSB2, TPSAB1, CPA3, and HPGDS). MC density was significantly greater in ccRCC tissues than in normal tissues, but MC activation characteristics were not significantly different between ccRCC and normal tissues.Activated and resting MCs were defined as having high and low expression of MC receptors and mediators, respectively, whereas proliferating MCs had high expression of proliferation-related genes. The overall percentage of activated MCs in ccRCC tissues did not change significantly but shifted toward a more activated subpopulation (VEGFA + MCs), with a concomitant decrease in proliferative MCs (TNF + MCs) and resting MCs. An analysis of the ratio of TNF + /VEGFA + MCs in tumors revealed that MCs exerted antitumor effects on ccRCC. However, VEGFA + MC was produced in large quantities in ccRCC tissues and promoted tumor angiogenesis compared with adjacent normal tissues, which aroused our concern. In addition, MC signature genes were associated with a better prognosis in the KIRC patient cohort in the TCGA database, which is consistent with our findings. Furthermore, the highest level of IL-1B expression was observed in macrophages in ccRCC samples, and spatial transcriptome analysis revealed the colocalization of VEGFA + MCs with IL1B + macrophages at the tumor-normal interface. In conclusion, this study revealed increased MC density in ccRCC. Although the proportion of activated MCs was not significantly altered in ccRCC tissues compared with normal tissues, this finding highlights a shift in the MC phenotype from CTSG high MCs to more activated VEGFA + MCs, providing a potential therapeutic target for inhibiting ccRCC progression.

    Keywords: mast cell, Clear cell renal cell carcinoma, single-cell RNA sequencing, heterogeneity, Spatial transcriptomics, prognosis

    Received: 10 Sep 2024; Accepted: 12 Dec 2024.

    Copyright: © 2024 Song and Jiao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiyu Song, Air Force Medical University, Xi'an, China
    Jianhua Jiao, Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China

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