Single-cell RNA sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue identified multi-ciliary cells in breast cancer DOI Creative Commons
Silvia González-Martínez, Irene Carretero‐Barrio, Belén Perez‐Mies

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Abstract The purpose of this study was to evaluate the suitability paraffin-embedded (FFPE) samples and fixed fresh (FF) for single-cell RNA sequencing (scRNAseq). To end, we compared whether profiles from FFPE matched FF tissue one invasive carcinoma no especial type (invasive ductal –IDC) lobular (ILC) were similar when captured using common immunohistochemical (IHC) immune features tumors. derived libraries showed high-quality parameters. cell heterogeneity obtained similar, although, there some differences in number cells captured, but specific populations exclusively by two different approaches. combined analysis four identified six types epithelial (normal basal cells, subpopulations neoplastic IDC ILC), tumoral microenvironment populations. scRNAseq results concordant with IHC markers. In addition, after quantitative assessment whole slide images QuPath, proportion IHQ sections those scRNAseq. Confirming tissue, technique subpopulation present only IDC, characterized expression genes related multi-ciliated (MCC) differentiation ( FOXJ1, ROPN1L, TPPP3, CFAP45 ). FOXJ1 confirmed presence positive a that Analysis cohort 214 ER-positive carcinomas demonstrated protein at least 1% 33% tumors, suggesting frequent focal MCC differentiation. Our support breast cancer.

Language: Английский

Single-Cell RNA Sequencing on Formalin-Fixed and Paraffin-Embedded (FFPE) Tissue Identified Multi-Ciliary Cells in Breast Cancer DOI Creative Commons
Silvia González-Martínez, José Palacios, Irene Carretero‐Barrio

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 197 - 197

Published: Jan. 29, 2025

The purpose of this study was to evaluate the suitability formalin-fixed and paraffin-embedded (FFPE) samples fixed fresh (FF) for single-cell RNA sequencing (scRNAseq). To end, we compared profiles from FFPE matched FF tissue one invasive carcinoma no special type (invasive ductal carcinoma-IDC) lobular (ILC) assess consistency in cell distribution molecular profiles. results were validated using immunohistochemistry (IHC), fluorescence situ hybridization (FISH), electron microscopy. Additionally, immune proportions identified by IHC quantified QuPath scRNAseq results. FFPE- FF-derived libraries demonstrated high-quality metrics, cellular heterogeneity similar. No exclusive populations either approach. four analysis six types epithelial cells, as well tumoral microenvironment populations. neoplastic cells concordant with common markers. proportion sections similar those obtained scRNAseq. We a previously poorly recognized subpopulation multi-ciliated (MCCs) (FOXJ1, ROPN1L). Analysis FOXJ1 214 ER-positive carcinomas protein expression third tumors, suggesting frequent focal MCC differentiation. Our support tissue, breast cancer.

Language: Английский

Citations

0
Inhibiting CXCR4 reduces immunosuppressive effects of myeloid cells in breast cancer immunotherapy DOI Creative Commons
Nicholas G. Ciavattone,

Avinash S. Bevoor,

Alex P. Farfel

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 12, 2025

Patients with triple negative breast cancer (TNBC) show only modest response rates to immune checkpoint inhibitor immunotherapy, motivating ongoing efforts identify approaches boost efficacy. Using an immunocompetent mouse model of TNBC, we investigated combination therapy anti-PD-1 immunotherapy antibody plus balixafortide, a cyclic peptide CXCR4. Cell-based assays demonstrated that balixafortide functions as inverse agonist, establishing mode action distinct from most compounds targeting Combination significantly reduced growth orthotopic tumors and extended overall survival relative single agent or vehicle. Adding increased numbers tertiary lymphoid structures, marker local tumor responses associated favorable in TNBC. Single cell RNA sequencing revealed T exhaustion markers effector activity. also signatures immunosuppressive myeloid derived suppressor cells (MDSCs) tumors. MDSCs isolated mice treated showed inhibition proliferation following ex vivo stimulation. These studies demonstrate combining CXCR4 enhances supporting future clinical trials.

Language: Английский

Citations

0
Advancements in tumor-infiltrating lymphocytes: Historical insights, contemporary milestones, and future directions in oncology therapy DOI

Muhammad Talha Aizaz,

Alina Sami Khan, Maria Khan

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 202, P. 104471 - 104471

Published: Aug. 8, 2024

Language: Английский

Citations

2
Heterogeneity of tertiary lymphoid structures predicts the response to neoadjuvant therapy and immune microenvironment characteristics in triple-negative breast cancer DOI
Qing Wang, Yushuai Yu, Chenxi Wang

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Language: Английский

Citations

2
Tumor-Infiltrating Lymphocyte Scoring in Neoadjuvant-Treated Breast Cancer DOI Open Access
Noémie Thomas, Soizic Garaud,

Mireille Langouo

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2895 - 2895

Published: Aug. 20, 2024

Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring prognostic and adds predictive value to residual burden evaluation after NAC. However, NAC induces changes in tumor, reliability post-NAC samples has not yet been studied. H&E- dual CD3/CD20 chromogenic IHC-stained tissues were scored stromal intra-tumoral by two experienced pathologists on pre- post-treatment BC tissues. Digital was performed using HALO

Language: Английский

Citations

1
Multimodal Spatial Proteomic Profiling in Acute Myeloid Leukemia DOI Creative Commons
Christopher Ly, Ivo Veletić,

Christopher D. Pacheco

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Abstract Acute myeloid leukemia (AML) resides in an immune rich microenvironment, yet, immune-based therapies have faltered eliciting durable responses. Bridging this paradox requires a comprehensive understanding of leukemic interactions within the bone marrow microenvironment. We optimized high-throughput tissue-microarray based pipeline for high-plex spatial immunofluorescence and mass cytometry imaging on single slide, capturing immune, tumor, structural components. Using unbiased clustering K function, we unveiled presence tertiary lymphoid-like aggregates which validated using transcriptomics independent proteomics approach. then found TLS signatures predictive outcomes AML integrated public 480 patient transcriptomic dataset. By harnessing proteomics, open possibility discovering novel structures that underpin response. Further, our study’s methodologies resources can be adapted other diseases where decalcification autofluorescence present challenges.

Language: Английский

Citations

0
Single-cell RNA sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue identified multi-ciliary cells in breast cancer DOI Creative Commons
Silvia González-Martínez, Irene Carretero‐Barrio, Belén Perez‐Mies

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Abstract The purpose of this study was to evaluate the suitability paraffin-embedded (FFPE) samples and fixed fresh (FF) for single-cell RNA sequencing (scRNAseq). To end, we compared whether profiles from FFPE matched FF tissue one invasive carcinoma no especial type (invasive ductal –IDC) lobular (ILC) were similar when captured using common immunohistochemical (IHC) immune features tumors. derived libraries showed high-quality parameters. cell heterogeneity obtained similar, although, there some differences in number cells captured, but specific populations exclusively by two different approaches. combined analysis four identified six types epithelial (normal basal cells, subpopulations neoplastic IDC ILC), tumoral microenvironment populations. scRNAseq results concordant with IHC markers. In addition, after quantitative assessment whole slide images QuPath, proportion IHQ sections those scRNAseq. Confirming tissue, technique subpopulation present only IDC, characterized expression genes related multi-ciliated (MCC) differentiation ( FOXJ1, ROPN1L, TPPP3, CFAP45 ). FOXJ1 confirmed presence positive a that Analysis cohort 214 ER-positive carcinomas demonstrated protein at least 1% 33% tumors, suggesting frequent focal MCC differentiation. Our support breast cancer.

Language: Английский

Citations

0