TY - JOUR
T1 - Leveraging single-cell transcriptomic data to uncover immune suppressive cancer cell subsets in triple-negative canine breast cancers
AU - Kim, Myung Chul
AU - Borcherding, Nicholas
AU - Song, Woo Jin
AU - Kolb, Ryan
AU - Zhang, Weizhou
N1 - Publisher Copyright:
Copyright © 2024 Kim, Borcherding, Song, Kolb and Zhang.
PY - 2024
Y1 - 2024
N2 - Introduction: Single-cell RNA sequencing (scRNA-seq) has become an essential tool for uncovering the complexities of various physiological and immunopathological conditions in veterinary medicine. However, there is currently limited information on immune-suppressive cancer subsets in canine breast cancers. In this study, we aimed to identify and characterize immune-suppressive subsets of triple-negative canine breast cancer (TNBC) by utilizing integrated scRNA-seq data from published datasets. Methods: Published scRNA-seq datasets, including data from six groups of 30 dogs, were subjected to integrated bioinformatic analysis. Results: Immune modulatory TNBC subsets were identified through functional enrichment analysis using immune-suppressive gene sets, including those associated with anti-inflammatory and M2-like macrophages. Key immune-suppressive signaling, such as viral infection, angiogenesis, and leukocyte chemotaxis, was found to play a role in enabling TNBC to evade immune surveillance. In addition, interactome analysis revealed significant interactions between distinct subsets of cancer cells and effector T cells, suggesting potential T-cell suppression. Discussion: The present study demonstrates a versatile and scalable approach to integrating and analyzing scRNA-seq data, which successfully identified immune-modulatory subsets of canine TNBC. It also revealed potential mechanisms through which TNBC promotes immune evasion in dogs. These findings are crucial for advancing the understanding of the immune pathogenesis of canine TNBC and may aid in the development of new immune-based therapeutic strategies.
AB - Introduction: Single-cell RNA sequencing (scRNA-seq) has become an essential tool for uncovering the complexities of various physiological and immunopathological conditions in veterinary medicine. However, there is currently limited information on immune-suppressive cancer subsets in canine breast cancers. In this study, we aimed to identify and characterize immune-suppressive subsets of triple-negative canine breast cancer (TNBC) by utilizing integrated scRNA-seq data from published datasets. Methods: Published scRNA-seq datasets, including data from six groups of 30 dogs, were subjected to integrated bioinformatic analysis. Results: Immune modulatory TNBC subsets were identified through functional enrichment analysis using immune-suppressive gene sets, including those associated with anti-inflammatory and M2-like macrophages. Key immune-suppressive signaling, such as viral infection, angiogenesis, and leukocyte chemotaxis, was found to play a role in enabling TNBC to evade immune surveillance. In addition, interactome analysis revealed significant interactions between distinct subsets of cancer cells and effector T cells, suggesting potential T-cell suppression. Discussion: The present study demonstrates a versatile and scalable approach to integrating and analyzing scRNA-seq data, which successfully identified immune-modulatory subsets of canine TNBC. It also revealed potential mechanisms through which TNBC promotes immune evasion in dogs. These findings are crucial for advancing the understanding of the immune pathogenesis of canine TNBC and may aid in the development of new immune-based therapeutic strategies.
KW - dog
KW - immune checkpoint genes
KW - interactome
KW - scRNA-seq
KW - triple-negative breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85206086170&partnerID=8YFLogxK
U2 - 10.3389/fvets.2024.1434617
DO - 10.3389/fvets.2024.1434617
M3 - Article
AN - SCOPUS:85206086170
SN - 2297-1769
VL - 11
JO - Frontiers in Veterinary Science
JF - Frontiers in Veterinary Science
M1 - 1434617
ER -