A single cell and spatial genomics atlas of human skin fibroblasts in health and disease DOI Creative Commons
Lloyd Steele, Chloe Admane,

Keerthi Priya Chakala

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 23, 2024

Abstract Fibroblasts are critical cells that shape the architecture and cellular ecosystems in multiple tissues. Understanding fibroblast heterogeneity their spatial context health disease has enormous clinical relevance. In this study, we constructed a spatially-resolved atlas of human skin fibroblasts from healthy 23 disorders. We define 6 major populations further three disease-specific subtypes, demonstrate composition different types disease. characterise human-specific fibroblastic reticular cell (FRC)-like subtype perivascular niche postulate origin prenatal lymphoid tissue organiser (LTo)-like cells. also show inflammatory myofibroblasts ( IL11 + MMP1 CXCL5 IL7R+ ) conserved disorders cancers across provide harmonised nomenclature for integrates previous findings other

Язык: Английский

Cancer associated fibroblasts in cancer development and therapy DOI Creative Commons

Hongyuan Jia,

Xingmin Chen,

Linling Zhang

и другие.

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Март 28, 2025

Cancer-associated fibroblasts (CAFs) are key players in cancer development and therapy, they exhibit multifaceted roles the tumor microenvironment (TME). From their diverse cellular origins, CAFs undergo phenotypic functional transformation upon interacting with cells presence can adversely influence treatment outcomes severity of cancer. Emerging evidence from single-cell RNA sequencing (scRNA-seq) studies have highlighted heterogeneity plasticity CAFs, subtypes identifiable through distinct gene expression profiles properties. multiple mechanisms, including regulation extracellular matrix (ECM) remodeling, direct promotion growth provision metabolic support, promoting epithelial-mesenchymal transition (EMT) to enhance invasiveness growth, as well stimulating stem cell properties within tumor. Moreover, induce an immunosuppressive TME contribute therapeutic resistance. In this review, we summarize fundamental knowledge recent advances regarding focusing on sophisticated potential targets. We discuss various strategies target ECM modulation, elimination, interruption CAF-TME crosstalk, CAF normalization, approaches developing more effective treatments. An improved understanding complex interplay between is crucial for new targeted therapies

Язык: Английский

Процитировано

4
Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects DOI Creative Commons
Alberto L. Horenstein, Angelo Corso Faini, Fabio Morandi

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 12, 2025

Monoclonal antibody therapy using CD38 as a target remains central to managing human multiple myeloma (MM). was selected early on for mAb-mediated MM, driven by findings from an Cluster of Differentiation (CD) Workshop. The first CD38-targeting be approved yielded strong trial results, significantly improving survival rates and earning widespread patient acceptance. However, resistance the later emerged, complicating treatment management. Despite CD38’s still role in MM therapy, too little attention has been paid its broader roles–not only marker but also enzyme adhesion molecule physiology. This review, collaborative effort between basic scientists clinical experts, explores some lesser-known mechanisms action interactions with at key stages treatment. review highlights relevance environment, focusing importance bone marrow (BM) niche. goal is identify new agents whose unique properties may enhance tumor eradication. By gaining deeper understanding therapeutic antibodies, cells, microenvironment (TME), it hoped that previously unrecognized vulnerabilities within disease revealed, paving way more effective strategies.

Язык: Английский

Процитировано

2
Overcoming cancer treatment resistance: unraveling the role of cancer-associated fibroblasts DOI Creative Commons
Xiaoyuan Wang, Yinuo Zhou,

Yingzhuo Wang

и другие.

Journal of the National Cancer Center, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Targeting myofibroblastic cancer-associated fibroblasts (myCAFs): a promising strategy for overcoming tumor progression and immunotherapy resistance DOI Creative Commons

Danting Wang,

Zhigang Chen

Visualized Cancer Medicine, Год журнала: 2025, Номер 6, С. 4 - 4

Опубликована: Янв. 1, 2025

Cancer-associated fibroblasts (CAFs), as the dominant stromal cell population in tumor microenvironment (TME), exhibit substantial heterogeneity, with subtypes such myofibroblastic cancer-associated (myCAFs) and inflammatory (iCAFs) playing distinct roles cancer progression. MyCAFs, defined by elevated ACTA2 expression, are particularly significant promoting growth, remodeling stroma, contributing to an immunosuppressive TME. Despite advances understanding CAF precise role of myCAFs invasion, metastasis, resistance therapies, especially immunotherapy, remains underexplored. This perspective highlights recent insights into myCAF functions within TME, emphasizing their potential therapeutic targets. By disrupting formation or combining myCAF-targeting approaches there is a promise for improving treatment outcomes overcoming immunotherapy cancer.

Язык: Английский

Процитировано

1
Fibroblast hierarchy dynamics during mammary gland morphogenesis and tumorigenesis DOI Creative Commons
Rosa Pascual, Jinming Cheng,

A. Smet

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 11, 2025

Abstract Fibroblasts form a major component of the stroma in normal mammary tissue and breast tumors. Here, we have applied longitudinal single-cell transcriptome profiling >45,000 fibroblasts mouse gland across five different developmental stages during oncogenesis. In gland, diverse stromal populations were resolved, including lobular-like fibroblasts, committed preadipocytes adipogenesis-regulatory, as well cycling puberty pregnancy. These specialized cell types appear to emerge from CD34 high mesenchymal progenitor cells, accompanied by elevated Hedgehog signaling. During late tumorigenesis, heterogeneous cancer-associated (CAFs) identified models cancer, population – myofibroblastic CAFs (myCAFs) that transcriptionally phenotypically similar senescent CAFs. Moreover, Wnt9a was demonstrated be regulator senescence myCAFs. findings reflect hierarchically organized compartment provides framework better understand cancerous states.

Язык: Английский

Процитировано

1
From darkness to light: Targeting CAFs as a new potential strategy for cancer treatment DOI
Dong Hua, Weijing Wang, Shuai Liang

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113482 - 113482

Опубликована: Окт. 30, 2024

Язык: Английский

Процитировано

6
Age-dependent differences in breast tumor microenvironment: challenges and opportunities for efficacy studies in preclinical models DOI Creative Commons
Paolo Falvo,

Stephan Gruener,

Stefania Orecchioni

и другие.

Cell Death and Differentiation, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Abstract Immunity suffers a function deficit during aging, and the incidence of cancer is increased in elderly. However, most models employ young mice, which are poorly representative adult patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine generation TCF1 + -stem-cell-like T cells (scTs) cyclophosphamide significantly improved anti-PD-1 efficacy anti-PD1-resistant like Triple-Negative Breast Cancer (TNBC) Non-Hodgkin’s Lymphoma (NHL), due to T-cell-mediated tumor killing. Here, we describe effect TT on TNBC growth tumor-microenvironment (TME) (6–8w, human puberty) versus (12 m, 40y-humans) mice. TT-efficacy was similar adults, as CD8 scTs were only marginally reduced adults. single-cell analyses revealed major differences TME: adults had fewer CD4 scTs, B-naïve NK-cells, more memory-B-cells. Cancer-associated-fibroblasts (CAF) with an Extracellular Matrix (ECM) deposition-signature (Matrix-CAFs) common while pro-inflammatory stromal populations myofibroblasts represented Matrix-CAFs mice displayed decreased ECM-remodeling abilities, collagen deposition, different pattern interactions other TME. Taken together, our results suggest age-dependent TME should be considered when designing preclinical studies.

Язык: Английский

Процитировано

0
SERPINH1 secretion by cancer-associated fibroblasts promotes hepatocellular carcinoma malignancy through SENP3-mediated SP1/SQLE pathway DOI
Hua Xiao,

Zhaoying Yao,

Tao Li

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 150, С. 114259 - 114259

Опубликована: Фев. 12, 2025

Язык: Английский

Процитировано

0
Single‐Cell Transcriptomic Analysis Reveals an Aggressive Basal‐Like Tumor Cell Subpopulation Associated With Poor Prognosis in Intrahepatic Cholangiocarcinoma DOI

Changyi Liao,

Yuting Zhang, Jing Yang

и другие.

Journal of Gastroenterology and Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 24, 2025

ABSTRACT Background and Aim Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer whose incidence increasing globally. However, high tumor heterogeneity of ICC restricts efficacy available systematic therapies. We aim to dissect utilizing high‐resolution single‐cell RNA sequencing identify novel therapeutic targets. Methods performed (scRNA‐seq) 26 samples from 23 patients spatial transcriptomic six sections patients. Bulk RNA‐seq data two public datasets were used for validation. Additionally, immunohistochemical staining multiplex immunofluorescence conducted validate infiltration distribution cells in microenvironment. Results discovered that malignant exhibited a remarkably degree heterogeneity. identified basal‐like cell subpopulation characterized by expression basal epithelial related genes including KRT5, KRT6A, KRT17. The was activation MET signaling extracellular matrix organization associated with invasion correlated poor prognosis. Cell–cell communication analysis further showed significant HGF‐MET interaction between inflammatory cancer–associated fibroblasts (iCAFs) cells. found iCAFs major source HGF environment contributed phenotype formation axis. Conclusions an aggressive subpopulation, which prognosis ICC. pathway contributes aggressiveness serves as target

Язык: Английский

Процитировано

0
A highly resolved integrated single-cell atlas of HPV-negative head and neck cancer DOI Creative Commons
Lina Kroehling, Andrew Chen,

Anthony Spinella

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Head and Neck Squamous Cell Carcinomas (HNSCC) are the seventh most prevalent form of cancer associated with human papilloma virus infection (HPV-positive) or tobacco alcohol use (HPV-negative). HPV-negative HNSCCs have a high recurrence rate, individual patients’ responses to treatment vary greatly due level cellular heterogeneity tumor its microenvironment. Here, we describe HNSCC single cell atlas, which created by integrating six publicly available datasets encompassing over 230,000 cells across 54 patients. We contextualized relationships between existing signatures populations, identified new subpopulations, show power this large-scale resource robustly identify associations transcriptional clinical phenotypes that would not be possible discover using fewer reveal previously undefined myeloid population, sex-associated changes in type proportions, novel interactions CXCL8-positive fibroblasts vascular endothelial cells. Beyond our findings, atlas will serve as public for high-resolution characterization HNSCC.

Язык: Английский

Процитировано

0