Single-cell Atlas reveals core function of CPVL/MSR1 expressing macrophages in the prognosis of triple-negative breast cancer DOI Creative Commons

Xin’an Wang,

Lin Li, Xue Zhang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 24, 2024

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer, with worst prognosis among all subtypes. The impact distinct cell subpopulations within tumor microenvironment (TME) on TNBC patient has yet to be clarified. Methods Utilizing single-cell RNA sequencing (scRNA-seq) integrated bulk (bulk RNA-seq), we applied Cox regression models compute hazard ratios, and cross-validated prognostic scoring using a GLMNET-based model. Cell communication analysis was used elucidate potential mechanisms CPVL MSR1. Ultimately, interference-mediated gene knockdown utilized validate specific genes polarization tumor-associated macrophages (TAMs). Results Our findings revealed that function immune cells more pivotal in prognosis, TAMs showing strongest correlation outcomes, compared other cells. Additionally, identified MSR1 as critical TAMs, expression positively correlated favorable outcomes associated poorer prognosis. Mechanistically, may contribute by inhibiting SPP1-CD44 ligand-receptor promoting CXCL9-CXCR3, C3-C3AR1 ligand-receptor, through which interact such monocytes, neutrophils, T Moreover, cytokines including IL-18, IFNγR1, CCL20, CCL2, along complement-related like TREM2 complement component CFD, participate process or regulating macrophage polarization. Furthermore, RT-PCR experiments confirmed M1-like TAM polarization, while linked M2-like Finally, significance these two also validated HER2-positive Conclusions are biomarkers for macrophage-mediated suggesting therapeutic targeting TNBC.

Language: Английский

Emerging nanoplatforms towards microenvironment-responsive glioma therapy DOI

Nigam Sekhar Tripathy,

Liza Sahoo,

Safal Kumar Paikray

et al.

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(2)

Published: Jan. 15, 2025

Language: Английский

Citations

0
The role of macrophages in liver metastasis: mechanisms and therapeutic prospects DOI Creative Commons
Qin Yuan,

Linlin Jia,

Jiahua Yang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Metastasis is a hallmark of advanced cancer, and the liver common site for secondary metastasis many tumor cells, including colorectal, pancreatic, gastric, prostate cancers. Macrophages in microenvironment (TME) promote cell through various mechanisms, angiogenesis immunosuppression, play unique role development metastasis. are affected by variety factors. Under conditions hypoxia increased acidity TME, more factors now found to polarization macrophages M2 type, exosomes amino acids. M2-type secretion such as VEGF, IL-1β, TGF-β1. subjected multiple regulatory mechanisms. They also interact with cells within co-regulate certain conditions, creation an immunosuppressive microenvironment. This interaction promotes metastasis, drug resistance, immune escape. Based on advent single-cell sequencing technology, further insights into macrophage subpopulations may help exploring new therapeutic targets future. In this paper, we will focus how affect well other each other, investigate mechanisms involved their potential targets.

Language: Английский

Citations

0
Molecular biology of the deadliest cancer – glioblastoma: what do we know? DOI Creative Commons

A Kh Ismaĭlov,

Aldo Spallone, Alexey A. Belogurov

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 21, 2025

Glioblastomas are the most prevalent primary brain tumors and associated with a dramatically poor prognosis. Despite an intensive treatment approach, including maximal surgical tumor removal followed by radio- chemotherapy, median survival for glioblastoma patients has remained around 18 months decades. Glioblastoma is distinguished its highly complex mechanisms of immune evasion pronounced heterogeneity. This variability apparent both within itself, which can exhibit multiple phenotypes simultaneously, in surrounding microenvironment. Another key feature “cold” microenvironment, characterized robust immunosuppression. Recent advances single-cell RNA sequencing have uncovered new promising insights, revealing previously unrecognized aspects this tumor. In review, we consolidate current knowledge on cells emphasis their biological properties unique patterns molecular communication through signaling pathways. The evidence underscores critical need personalized poly-immunotherapy other approaches to overcome plasticity stem cells. Analyzing microenvironment individual using transcriptomics implementing customized immunotherapeutic strategy could potentially improve outcomes those facing formidable disease.

Language: Английский

Citations

0
CD105+ fibroblasts support an immunosuppressive niche in women at high risk of breast cancer initiation DOI
Eric G. Carlson, Jennifer C. Lopez, Yukiko Yamaguchi

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Aging is the greatest risk factor for breast cancer, and although epithelial cells are source of carcinomas, changes alone do not fully explain cancer susceptibility. Fibroblasts macrophages key stromal constituents around origin in tissue. With age, surrounding terminal ductal lobular units (TDLUs) become increasingly immunosuppressive. CD105 + fibroblasts intercalate within TDLUs, drive luminal differentiation, give rise to immunosuppressive cancer-associated other tissues. We propose that differences a crucial component stroma shapes Primary fibroblast cultures were established from prophylactic reduction mammoplasties women ranging age 16 70 years ( BRCA1 mutation carriers). Growth characteristics, transcriptional profiles, differentiation potential, secreted proteins profiled subtypes diverse donors. Co-cultures with fibroblasts, monocytes, macrophages, T used ascertain functional role played by immune cell modulation. found peri-epithelial enriched older as well who carry mutations. These exhibit robust adipogenesis secrete factors related macrophage polarization. Macrophages cocultured better maintain or enhance polarization states than media alone. increased expression genes. supported anti-inflammatory macrophage-mediated suppression proliferation, whereas - significantly reduced suppressive effect on proliferation. Establishment coculture system dissect molecular circuits between has broad utility understanding mammary gland development events precede initiation. may coordinate suppress immunosurveillance increase

Language: Английский

Citations

0
Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas DOI Creative Commons
Yongtao Yang,

Yingzhou Hong,

Kai Zhao

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Oct. 24, 2024

Introduction Diffuse high-grade gliomas are the most common malignant adult neuroepithelial tumors in humans and a leading cause of cancer-related death worldwide. The advancement high throughput transcriptome sequencing technology enables rapid comprehensive acquisition data from target cells or tissues. This aids researchers understanding identifying critical therapeutic targets for prognosis treatment diffuse glioma. Methods Spatial transcriptomics was conducted on two cases isocitrate dehydrogenase (IDH) wild-type glioma (Glio-IDH-wt) IDH-mutant (Glio-IDH-mut). Gene set enrichment analysis clustering were employed to pinpoint differentially expressed genes (DEGs) involved progression gliomas. spatial distribution DEGs spatially defined regions human tissues overlaid t-distributed stochastic neighbor embedding (t-SNE) plots. Results We identified total 10,693 DEGs, with 5,677 upregulated 5,016 downregulated, Specifically, SPP1 , IGFBP2 CALD1 TMSB4X exhibited expression carcinoma both Glio-IDH-wt Glio-IDH-mut, 3 ( SMOC1 APOE HIPK2 ) 4 PPP1CB UBA52 S100A6 CTSB only tumor respectively. Moreover, Kyoto Encyclopedia Genes Genomes (KEGG) gene ontology (GO) analyses revealed that closely related PI3K/Akt signaling pathway, virus infection, cytokine-cytokine receptor interaction. Importantly, these validated using GEPIA databases. Furthermore, study patterns key regulatory genes, including those protein post-translational modification RNA binding protein-encoding Discussion is one breakthroughs field medical biotechnology as this can map analytes such information their physical location tissue sections. Our findings illuminate previously unexplored profiles biomarkers glioma, offering novel insight development strategies

Language: Английский

Citations

1
Lithium-induced apoptotic cell death is not accompanied by a noticeable inflammatory response in the kidney DOI Creative Commons
Irina Baranovskaya,

Kevin Volk,

Sati Alexander

et al.

Frontiers in Physiology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 14, 2024

Lithium (Li + ) therapy is a valuable tool in psychiatric practice that remains underutilized due to safety concerns. Excessive plasma Li levels are nephrotoxic and can trigger local immune response. Our understanding of the immunomodulatory effects kidney fragmentary. Here, we studied how mechanisms contribute development -induced adverse kidneys C57BL/6NJ mice placed on 0.3% lithium carbonate diet for 28 days. We combined histochemical techniques, immunoblotting, flow cytometry, qPCR proteome profiler arrays characterize renal tissue damage, infiltrating cells cytokine markers, activation pyroptotic apoptotic cascades receiving -containing regular diets. found biomarkers tubular injury marker, KIM-1, neutrophil gelatinase-associated lipocalin, NGAL, were elevated -treated when compared controls. This correlated with increased interstitial fibrosis mice. Administration did not activate pro-inflammatory NLRP3 inflammasome cascade but promoted apoptosis tissue. The TUNEL-positive signal pro-apoptotic proteins, Bax, cleaved caspase-3, caspase-8, observed significantly higher abundance CD93, CCL21, fractalkine, accumulation F4.80 macrophages reduced M1/M2 polarization ratio decreased CD4 Therefore, after days treatment, insult manifests facilitated cell death without an evident

Language: Английский

Citations

0
Prognostic Modeling and Emerging Therapeutic Targets Unveiled through Single-Cell Sequencing in Esophageal Squamous Cell Carcinoma DOI Creative Commons

B H Pan,

Haochun Shi, Guangyao Shan

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(19), P. e38078 - e38078

Published: Sept. 21, 2024

Language: Английский

Citations

0
Single-cell Atlas reveals core function of CPVL/MSR1 expressing macrophages in the prognosis of triple-negative breast cancer DOI Creative Commons

Xin’an Wang,

Lin Li, Xue Zhang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 24, 2024

Background Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer, with worst prognosis among all subtypes. The impact distinct cell subpopulations within tumor microenvironment (TME) on TNBC patient has yet to be clarified. Methods Utilizing single-cell RNA sequencing (scRNA-seq) integrated bulk (bulk RNA-seq), we applied Cox regression models compute hazard ratios, and cross-validated prognostic scoring using a GLMNET-based model. Cell communication analysis was used elucidate potential mechanisms CPVL MSR1. Ultimately, interference-mediated gene knockdown utilized validate specific genes polarization tumor-associated macrophages (TAMs). Results Our findings revealed that function immune cells more pivotal in prognosis, TAMs showing strongest correlation outcomes, compared other cells. Additionally, identified MSR1 as critical TAMs, expression positively correlated favorable outcomes associated poorer prognosis. Mechanistically, may contribute by inhibiting SPP1-CD44 ligand-receptor promoting CXCL9-CXCR3, C3-C3AR1 ligand-receptor, through which interact such monocytes, neutrophils, T Moreover, cytokines including IL-18, IFNγR1, CCL20, CCL2, along complement-related like TREM2 complement component CFD, participate process or regulating macrophage polarization. Furthermore, RT-PCR experiments confirmed M1-like TAM polarization, while linked M2-like Finally, significance these two also validated HER2-positive Conclusions are biomarkers for macrophage-mediated suggesting therapeutic targeting TNBC.

Language: Английский

Citations

0