FA Metabolism and Male Breast Cancer
Summary
In this study, researchers analyzed cells from male and female breast cancer patients, uncovering pronounced cellular and immunological disparities between male breast cancer (MBC) and female breast cancer (FBC). MBC demonstrated diminished T cell presence, enhanced metastatic behaviors, and an activated fatty acid metabolism associated with metastasis and reduced immune detection. Furthermore, T cells in MBC showed indications of malfunction through the p38 MAPK and lipid oxidation pathways. In contrast, FBC T cells were marked by stronger immune reactions and increased cytotoxic marker activity. These findings shed light on the intricate relationship between cancer cells and T cells in MBC, deepening our understanding of its immune and metabolic characteristics.
Research Criteria
The article focuses on Male breast cancer (MBC) and its comparison with female breast cancer (FBC). The study aims to understand the tumor microenvironment and metabolism features of MBC to better comprehend the underlying mechanisms of MBC development. The research utilizes single-cell RNA sequencing (scRNA-seq) and scTCR-seq technology to explore the tumor microenvironment of breast cancer and compare the immunological and metabolic features between MBC and FBC samples.
Fig.1 Experimental design1.
Sample Type
Human breast cancer samples.
Result—MBC had Less Immunological Infiltration than FBC
In an intricate exploration of breast cancer's cellular diversity, researchers integrated scRNA-seq data from both male (MBC) and female (FBC) breast cancer samples, ensuring all were ER-positive and that clinical characteristics, such as tumor stage, did not skew results. Their comprehensive analysis, depicted in detailed figures, discerned various cell types within the breast cancer ecosystem, from epithelial cells to various endothelial cells. Notably, the chromosomal landscape inferred from the data enabled the differentiation of malignant epithelial cells from non-malignant microenvironment cells. A salient observation emerged: MBC displayed a markedly higher proportion of cancer cells and a diminished presence of immune cells, particularly T and B cells, signifying a reduced level of immune infiltration compared to FBC. This phenomenon was consistently corroborated through scRNA-seq, bulk transcriptome, and immunohistochemistry analyses, underscoring MBC's distinctively lower immune infiltration, especially in T and B cells, relative to FBC.
Fig.2 Cellular components of MBC and FBC samples were compared1.
Result—MBC and FBC T Cell Subpopulations have Different Functional Properties
Researchers have unveiled distinct functional disparities in T cell subpopulations between male breast cancer (MBC) and female breast cancer (FBC) samples. Through unsupervised clustering analysis, 13 unique clusters were identified, encompassing various CD8+, CD4+, and NKT cell clusters, each characterized by specific marker genes. The CD8+ KRT8+ cluster was predominantly observed in MBC samples, while the CD4+ CXCL13+ Th cells were conspicuously absent, suggesting potential resistance in MBC to immunotherapies targeting PD1 or CTLA4. Integrating scRNA-seq and scTCR-seq data revealed larger clone sizes in certain CD8+ T cells in MBC compared to FBC. Additionally, the p38 MAPK signature, indicative of CD8+ T cell senescence, was markedly elevated in MBC. Transcriptional patterns highlighted that MBC T cells exhibited heightened lipid oxidation, a hallmark of dysfunction, influenced by lipid metabolism. Conversely, FBC T cells displayed active cytotoxicity, underscored by the expression of specific cytotoxic T-cell markers and immune-modulatory cytokine pathways. This study elucidates the nuanced differences in T cell functionality between MBC and FBC, spotlighting potential therapeutic implications.
Fig.3 Characterization of T cell subpopulations and clone sizes in MBC and FBC samples using scRNA-seq and scTCR-seq1.
Creative Biolabs' Services
Single Cell RNA Sequencing Service
In our pursuit of unraveling the intricacies within heterogeneous cell populations, we acknowledge their inherent lack of homogeneity and synchronization in characteristics. Our comprehensive suite of services encompasses the entire single-cell RNA sequencing process, spanning sample preparation, library construction, and data analysis. This holistic approach not only enhances project adaptability, velocity, and data precision but also enables us to explore the multifaceted transcriptome diversity concealed within these complex samples.
Learn more
Single Cell TCR Profiling Service
At Creative Biolabs, we proudly deliver a vast array of bespoke, top-tier services within the realm of single-cell TCR profiling. These meticulously crafted offerings serve as our unwavering commitment to bolstering worldwide scientific endeavors in immunology and the interconnected biomedical sector. Our profound expertise shines in unraveling the intricate landscape of immune receptor cartography and unearthing novel biomarkers, underpinning our unwavering dedication to advancement.
Learn moreCreative Biolabs offers a comprehensive suite of single-cell analytical solutions encompassing single-cell RNA sequencing and single-cell TCR profiling. Our single-cell RNA sequencing empowers in-depth exploration of gene expression at the granularity of individual cells, unraveling profound insights into cellular diversity and functionality. Meanwhile, our single-cell TCR profiling delivers meticulous T-cell receptor characterization, enabling the detection of elusive T-cell subsets and immune responses. Armed with state-of-the-art technology and a cadre of seasoned scientists, we deliver top-tier data and invaluable scientific insights, facilitating cutting-edge research and drug development endeavors.
For any information, please contact us.
Reference
- Sun, Handong, et al. "Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer." Nature Communications 14.1 (2023): 5590.
