Cancer Letters, Год журнала: 2025, Номер unknown, С. 217475 - 217475
Опубликована: Янв. 1, 2025
Язык: Английский
Cell Discovery, Год журнала: 2023, Номер 9(1)
Опубликована: Март 6, 2023
Hepatocellular carcinoma (HCC) is an immunotherapy-resistant malignancy characterized by high cellular heterogeneity. The diversity of cell types and the interplay between tumor non-tumor cells remain to be clarified. Single RNA sequencing human mouse HCC tumors revealed heterogeneity cancer-associated fibroblast (CAF). Cross-species analysis determined prominent CD36+ CAFs exhibited high-level lipid metabolism expression macrophage migration inhibitory factor (MIF). Lineage-tracing assays showed CD36+CAFs were derived from hepatic stellate cells. Furthermore, CD36 mediated oxidized LDL uptake-dependent MIF via peroxidation/p38/CEBPs axis in CAFs, which recruited CD33+myeloid-derived suppressor (MDSCs) MIF- CD74-dependent manner. Co-implantation with promotes progression vivo. Finally, inhibitor synergizes anti-PD-1 immunotherapy restoring antitumor T-cell responses HCC. Our work underscores importance elucidating function specific CAF subset understanding microenvironment immune system.
Язык: Английский
Процитировано
158
Cell Death and Disease, Год журнала: 2023, Номер 14(9)
Опубликована: Сен. 4, 2023
Abstract The tumor microenvironment (TME) is made up of cells and extracellular matrix (non-cellular component), cellular components include cancer non-malignant such as immune stromal cells. These three types establish complex signals in the body further influence genesis, development, metastasis participate resistance to anti-tumor therapy. It has attracted scholars study TME due significant efficacy checkpoint inhibitors (ICI) chimeric antigen receptor T (CAR-T) solid tumors hematologic tumors. After more than 10 years efforts, role strategy treating based on have developed rapidly. Moreover, ICI been recommended by guidelines first- or second-line treatment strategies a variety At same time, another major class TME, which also play very important metabolism, growth, metastasis, evasion resistance. Stromal can be recruited from neighboring non-cancerous host formed transdifferentiation they development drug secreting various factors exosomes, participating angiogenesis regulating response matrix. However, with deepening understanding cells, people found that not only effect promoting but inhibit some cases. In this review, we will introduce origin well specific mechanism tumorigenesis for We focus tumor-associated fibroblasts (CAFs), mesenchymal stem (MSCs), adipocytes (CAAs), endothelial (TECs) pericytes (PCs)
Язык: Английский
Процитировано
150
Nature Reviews Clinical Oncology, Год журнала: 2024, Номер 21(2), С. 147 - 164
Опубликована: Янв. 8, 2024
Язык: Английский
Процитировано
124
Molecular Cancer, Год журнала: 2022, Номер 21(1)
Опубликована: Дек. 22, 2022
Cancer divergence has many facets other than being considered a genetic term. It is tremendous challenge to understand the metastasis and therapy response in cancer biology; however, it postulates opportunity explore possible mechanism surrounding tumor environment. Most deadly solid malignancies are distinctly characterized by their microenvironment (TME). TME consists of stromal components such as immune, inflammatory, endothelial, adipocytes, fibroblast cells. stem cells (CSCs) or stem-like small sub-set population within believed be responsible player self-renewal, metastasis, The correlation between CSCs remains an enigma understanding events resistance biology. Recent evidence suggests that dictates maintenance arbitrate progression metastasis. adipocyte, release growth factors, cytokines, chemokines, microRNAs, exosomes provide cues for gain CSC features. These intricate cross-talks fueled evolve into aggressive, invasive, migratory phenotypes development. In this review, we have abridged recent developments role factors how these influence transition further translate cancer.
Язык: Английский
Процитировано
120
Molecular Cancer, Год журнала: 2023, Номер 22(1)
Опубликована: Фев. 10, 2023
Abstract In recent years, breakthroughs have been made in tumor immunotherapy. However, immunotherapy, particularly anti-PD-1/PD-L1 immune checkpoint inhibitors, is effective only a small percentage of patients solid cancer. How to improve the efficiency cancer immunotherapy an urgent problem be solved. As we all know, state microenvironment (TME) essential factor affecting effectiveness and cancer-associated fibroblasts (CAFs) TME attracted much attention years. one main components TME, CAFs interact with cells by secreting cytokines vesicles, participating ECM remodeling, finally response process. With in-depth study heterogeneity, new strategies are provided for finding targets combination predicting efficacy. this review, focus on role microenvironment, then further elaborate potential mechanisms pathways influencing addition, summarize clinical application value CAFs-related markers cancers.
Язык: Английский
Процитировано
113
Journal of Hepatology, Год журнала: 2022, Номер 77(3), С. 849 - 864
Опубликована: Май 18, 2022
Язык: Английский
Процитировано
98
Nature Reviews Gastroenterology & Hepatology, Год журнала: 2023, Номер 20(6), С. 349 - 365
Опубликована: Янв. 25, 2023
Язык: Английский
Процитировано
89
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Июль 5, 2024
Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.
Язык: Английский
Процитировано
81
Frontiers in Pharmacology, Год журнала: 2023, Номер 14
Опубликована: Март 14, 2023
Cancer immunotherapy has opened a new landscape in cancer treatment, however, the poor specificity and resistance of most targeted therapeutics have limited their therapeutic efficacy. In recent years, role CAFs immune regulation been increasingly noted as more evidence uncovered regarding link between cancer-associated fibroblasts (CAFs) evolutionary process tumor progression. interact with cells to shape microenvironment (TIME) that favors malignant progression, crosstalk leads failure immunotherapies. this review, we outline advances immunosuppressive function CAFs, highlight mechanisms CAFs-immune cell interactions, discuss current CAF-targeted strategies for future study.
Язык: Английский
Процитировано
54
Cellular and Molecular Gastroenterology and Hepatology, Год журнала: 2023, Номер 15(4), С. 985 - 999
Опубликована: Янв. 1, 2023
Primary liver cancer (PLC) includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma is the sixth most common worldwide with poor prognosis. PLC characterized by an abundant stromal reaction in which cancer-associated fibroblasts (CAFs) are one of major components. Solid evidence has demonstrated crucial role CAFs tumor progression, CAF abundance often correlated clinical outcomes. Although regarded as attractive promising target for treatment, a understanding origins heterogeneity lack specific markers hurdles to efficient CAF-specific therapy. In this review, we examine recent advances diversity context biomarkers, subtypes, functions PLC. The regulatory roles extracellular matrix remodeling, metastasis, stemness, therapeutic resistance summarized. With increasing link between reduced antitumor immune responses, provide updated knowledge on crosstalk cells within microenvironment, leads resistance. addition, present current CAF-targeted therapies describe some future perspectives. A better biology will shed light novel strategy against
Язык: Английский
Процитировано
49