CXCL12 alone is enough to Reprogram Normal Fibroblasts into Cancer-Associated Fibroblasts DOI Creative Commons
Zelong Ma,

Diping Yu,

Siqi Tan

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 8, 2025

Abstract Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing significant roles in regulating cancer progression. However, underlying mechanism CAFs activation remains elusive. In this study, we aim to investigates mechanisms by which promote conversion normal (NFs) lung cancer, with a focus on role p53 mutations and CXCL12/STAT3 signaling axis. We found that significantly induced NFs acquire properties (called CEFs), including upregulation α-SMA Vimentin, enhanced proliferation migration, increased ability cell migration. vivo, CEFs accelerated A549 xenograft growth spontaneous metastasis. CXCL12 was identified as key factor NFs-to-CEFs conversion, its expression positively correlated markers cancer. Further investigation confirmed is sufficient reprogram into through STAT3 pathway. Notably, inhibiting pathway reduced CAFs, thereby hindering progression both vitro vivo. Our study reveals could CAFs-like cells axis, enhancing metastasis Therefore, inhibition axis promising strategy for treatment cancers other CXCL12‐dependent malignancies.

Language: Английский

Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action DOI Creative Commons
Caitlin M. Tilsed, Scott Fisher, Anna K. Nowak

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: July 29, 2022

Chemotherapy has historically been the mainstay of cancer treatment, but our understanding what drives a successful therapeutic response remains limited. The diverse patients to chemotherapy attributed principally differences in proliferation rate tumor cells, there is actually very little experimental data supporting this hypothesis. Instead, other mechanisms at cellular level and composition microenvironment appear drive sensitivity. In particular, immune system critical determinant with depletion or knock-out key cell populations immunological mediators completely abrogating benefits pre-clinical models. perspective, we review literature regarding known action cytotoxic agents determinants from individual cells microenvironment. We then summarize current work toward development dynamic biomarkers for propose model sensitive

Language: Английский

Citations

94
Predictive biomarkers of colon cancer immunotherapy: Present and future DOI Creative Commons

Wanting Hou,

Yi Cheng, Hong Zhu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 22, 2022

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as first-line treatment metastatic MSI-H patients. Additionally, neoadjuvant immunotherapy presented efficacy in treating early-stage Although MSI been thought of an effective predictive biomarker immunotherapy, only a small proportion patients were MSI-H, certain intrinsic or acquired resistance to immunotherapy. Thus, further search biomarkers stratify is meaningful Except MSI, other biomarkers, such PD-L1 expression level, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), gut microbiota, ctDNA, circulating immune cells also proposed be correlated patient survival some studies. Moreover, developing new diagnostic techniques helps identify accurate this review, we outline reported discuss prospects technological changes development

Language: Английский

Citations

89
IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts DOI Creative Commons

Astrid Van den Eynde,

Laura Gehrcken,

Tias Verhezen

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Feb. 9, 2024

Abstract Background It remains challenging to obtain positive outcomes with chimeric antigen receptor (CAR)-engineered cell therapies in solid malignancies, like colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC). A major obstacle is the lack of targetable surface antigens that are not shared by healthy tissues. CD70 emerges as interesting target, due its stringent expression pattern tissue apparent role tumor progression a considerable amount malignancies. Moreover, also expressed on cancer-associated fibroblasts (CAFs), another roadblock for treatment efficacy CRC PDAC. We explored therapeutic potential target CAR natural killer (NK) therapy CRC, PDAC, focusing cells CAFs, lymphoma. Methods RNA-seq data immunohistochemical analysis patient samples were used explore PDAC patients. In addition, CD70-targeting NK developed assess cytotoxic activity against + effect cytokine stimulation their was evaluated. The vitro functionality CD70-CAR investigated panel CAF lines varying expression. Lymphoma-bearing mice validate vivo potency cells. Lastly, consider variability, tested patient-derived organoids containing CAFs. Results this study, we identified CAFs Functional evaluation CD70-directed indicated IL-15 essential effective elimination improve burden survival bearing tumors. Mechanistically, resulted improved upregulating increasing secretion pro-inflammatory cytokines, mainly autocrine or intracellular manner. Conclusions disclose an attractive both hematological armored act potent effectors eliminate these They can patients potentially other desmoplastic

Language: Английский

Citations

28
Construction of a novel cancer-associated fibroblast-related signature to predict clinical outcome and immune response in cervical cancer DOI Creative Commons

Zhongxuan Gui,

Yingquan Ye,

Yu Li

et al.

Translational Oncology, Journal Year: 2024, Volume and Issue: 46, P. 102001 - 102001

Published: June 7, 2024

This study developed a prognostic signature for cervical cancer using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), TISCH database, focusing on cancer-associated fibroblasts (CAFs). Through LASSO Cox regression integrated bioinformatics analyses, we identified 144 differentially expressed genes (DEGs) related to CAFs, which an 11-gene CAF-related (CAFRSig) was constructed. CAFRSig effectively stratified patients into high- low-risk categories, demonstrating significant capability in predicting overall survival. ontology (GO) gene set variation analysis (GSVA) linked the DEGs crucial pathways tumor malignancy, immune response, fatty acid metabolism. landscape analysis, utilizing TIMER platform CIBERSORT algorithm, revealed positive correlation between cell effector functions scores, highlighting model's potential identify likely respond checkpoint blockade (ICB) therapies. Furthermore, neuropilin 1 (NRP1), key CAFRSig, upregulated tissues associated with disease progression differentiation. downregulation of NRP1 curbed proliferation influenced epithelial-mesenchymal transition (EMT), implicating PI3K/AKT pathway modulating PD-L1 expression. comprehensive establishes robust based genes, offering valuable insights optimizing therapeutic strategies management.

Language: Английский

Citations

17
Targeting the devil: Strategies against cancer-associated fibroblasts in colorectal cancer DOI
Yuting Chen, Zhiyong Liang, Maode Lai

et al.

Translational research, Journal Year: 2024, Volume and Issue: 270, P. 81 - 93

Published: April 16, 2024

Language: Английский

Citations

12
Fight the Cancer, Hit the CAF! DOI Open Access
Andrea Papait, Jacopo Romoli, Francesca Romana Stefani

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(15), P. 3570 - 3570

Published: July 22, 2022

The tumor microenvironment (TME) is comprised of different cellular components, such as immune and stromal cells, which co-operate in unison to promote progression metastasis. In the last decade, there has been an increasing focus on one specific component TME, component, often referred Cancer-Associated Fibroblasts (CAF). CAF modulate response alter composition extracellular matrix with a decisive impact immunotherapies conventional chemotherapy. most recent publications based single-cell analysis have underlined heterogeneity unique plasticity that strongly TME. this review, we not only characterization findings, but also their system. We discuss clinical trials preclinical studies where targeting revealed controversial results. Therefore, future efforts should understanding functional properties individual subtypes CAF, taking into consideration peculiarities each pathological context.

Language: Английский

Citations

37
Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients DOI Creative Commons
Ran Zhang, Feng Liu

Journal of Translational Medicine, Journal Year: 2022, Volume and Issue: 20(1)

Published: Oct. 4, 2022

Cancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers.In order investigate CAF-related genes associated with construct gene signatures prostate cancer, we firstly established a radio-resistant CAF cell subline (referred as CAFR) from Mus-CAF CAF) through fractionated irradiation using X-rays. Transcriptome sequencing CAFR was conducted, 2626 differentially expressed (DEGs) were identified. Human homologous of mouse DEGs then obtained.Functional enrichment analysis revealed that these significantly enriched ECM- immune-related functions pathways. Based on GSE116918 dataset, 186 correlated biochemical recurrence-free survival (BCRFS) cancer patients, 16 which selected BCRFS-related signature, such ACPP, THBS2, KCTD14; 142 metastasis-free (MFS), used MFS-related HOPX, TMEM132A, ZNF467. Both Gene Expression Omnibus (GEO) The Cancer Genome Atlas (TCGA) datasets confirmed two predicted BCRFS MFS patients. scores higher patients gleason grades T stages. Moreover, signature an independent factor nomogram consisting various factors 2-, 3-, 5-year time Furthermore, score positively immune checkpoints.Our could predict undergoing radiotherapy.

Language: Английский

Citations

27
Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on T-cell marker genes to predict prognosis and therapeutic response in lung squamous cell carcinoma DOI Creative Commons
Xuezhong Shi, Ani Dong, Xiaocan Jia

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

Cancer immunotherapy is an increasingly successful strategy for treating patients with advanced or conventionally drug-resistant cancers. T cells have been proved to play important roles in anti-tumor and tumor microenvironment shaping, while these not explained lung squamous cell carcinoma (LUSC). In this study, we first performed a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from the gene expression omnibus (GEO) database identify 72 T-cell marker genes. Subsequently, constructed 5-gene prognostic signature training cohort based on genes cancer genome atlas (TCGA) database, which was further validated testing GEO cohort. The areas under receiver operating characteristic curve at 1-, 3-, 5-years were 0.614, 0.713 0.702 cohort, 0.669, 0.603 0.645 0.661, 0.628 0.590 respectively. Furthermore, created highly reliable nomogram facilitate clinical application. Gene set enrichment showed that immune-related pathways mainly enriched high-risk group. Tumor immune indicated group exhibited higher score, stromal infiltration levels. Moreover, checkpoints human leukocyte antigen family all overexpressed Drug sensitivity revealed low-risk sensitive 8 chemotherapeutic drugs 4 drugs. short, our study reveals novel genes, provides new target theoretical support LUSC patients.

Language: Английский

Citations

24
Cancer-Associated Fibroblasts: The Origin, Biological Characteristics and Role in Cancer—A Glance on Colorectal Cancer DOI Open Access

Charalampos Fotsitzoudis,

Asimina Koulouridi,

Ippokratis Messaritakis

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(18), P. 4394 - 4394

Published: Sept. 9, 2022

The therapeutic approaches to cancer remain a considerable target for all scientists around the world. Although new treatments are an everyday phenomenon, still remains one of leading mortality causes. Colorectal (CRC) in this category, although patients with CRC may have better survival compared other malignancies. Not only tumor but also its environment, what we call microenvironment (TME), seem contribute progression and resistance therapy. TME consists different molecules cells. Cancer-associated fibroblasts major component. They arise from normal cells through various pathways. Their role seems promotion, participating tumorigenesis, proliferation, growth, invasion, metastasis treatment. Different markers, such as a-SMA, FAP, PDGFR-β, periostin, been used detection cancer-associated (CAFs). is important two main reasons; research has shown that their existence correlated prognosis, they already under evaluation possible However, extensive warranted.

Language: Английский

Citations

23
Advancing translational research for colorectal immuno-oncology DOI Creative Commons
E Thomas, Josephine A. Wright, Stephen J. Blake

et al.

British Journal of Cancer, Journal Year: 2023, Volume and Issue: 129(9), P. 1442 - 1450

Published: Aug. 10, 2023

Abstract Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely respond those with DNA mismatch repair deficient (dMMR) microsatellite instability (MSI) However, reliable predictors ICI response lacking, even within dMMR/MSI subtype. This, together identification novel mechanisms increase rates prevent resistance, ongoing vitally important unmet needs. To address current challenges translation early research findings into therapeutic strategies, this review summarises present state preclinical testing used inform development immuno-regulatory treatment strategies for CRC. The shortfalls advantages commonly utilised mouse models CRC, including chemically induced, transplant transgenic approaches highlighted. Appropriate use existing models, incorporation patient-derived data cutting-edge recapitulate features human disease will be key accelerating clinically relevant area.

Language: Английский

Citations

14