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ORIGINAL RESEARCH article

Front. Vet. Sci.
Sec. Oncology in Veterinary Medicine
Volume 11 - 2024 | doi: 10.3389/fvets.2024.1434617
This article is part of the Research Topic Tumor Microenvironment Complexity and its Therapeutic Implications View all 6 articles

Leveraging single-cell transcriptomic data to uncover immune suppressive cancer cell subsets in triple-negative canine breast cancers

Provisionally accepted
Myung-Chul Kim Myung-Chul Kim 1*Nicholas Borcherding Nicholas Borcherding 2Woo-Jin Song Woo-Jin Song 1Ryan Kolb Ryan Kolb 3Weizhou Zhang Weizhou Zhang 3
  • 1 Jeju National University, Jeju City, Republic of Korea
  • 2 Division of Immunobiology, Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
  • 3 University of Florida, Gainesville, Florida, United States

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

    Single-cell RNA sequencing (scRNA-seq) has become an essential tool to unlock the secrets of various physiologic and immunopathological conditions in veterinary medicine. Currently, little information is available regarding the immune suppressive cancer subsets in canine breast cancers. Herein, we aimed to identify and characterize immune suppressive subsets of triple-negative canine breast cancer (TNBC) by leveraging scRNA-seq data integration from published datasets. Published scRNA-seq datasets, including 6 groups of 30 dogs, were subjected to integrated bioinformatic analysis. Immune modulatory TNBC subsets were identified by functional enrichment with immune-suppressive gene sets, including anti-inflammatory and M2-like macrophages. Leveraging viral infection, angiogenesis and leukocyte chemotaxis were identified to be the key genes and immune-suppressive signaling pathways for TNBC to evade immune surveillance. In addition, interactome analysis identified significant interactions between distinct subsets of cancer cells and effector T cells, suggesting T cell suppression. The present study demonstrates versatile and scalable scRNA-seq integration and analysis that identified canine TNBC subsets with immune modulatory capacity and revealed potential mechanisms by which TNBC induces immune evasion in dogs. The results of this study will be valuable in expediting the understanding of the immune pathogenesis of canine TNBC, contributing to the development of novel immune therapeutics.

    Keywords: dog, immune checkpoint genes, Interactome, ScRNA-seq, Triple-negative breast cancer

    Received: 18 May 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Kim, Borcherding, Song, Kolb and Zhang. 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: Myung-Chul Kim, Jeju National University, Jeju City, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.