Knockdown of liver cancer cell‐secreted exosomal PSMA5 controls macrophage polarization to restrain cancer progression by blocking JAK2/STAT3 signaling DOI Creative Commons
Shujie Xie, Xiang Li, Yan Jia

и другие.

Immunity Inflammation and Disease, Год журнала: 2024, Номер 12(2)

Опубликована: Фев. 1, 2024

Abstract Introduction Tumor‐associated macrophages, a major component of the tumor microenvironment, undergo polarization into M2 macrophages (M2), and thereby exert an immunosuppressive effect to induce cancer metastasis. This study strives uncover molecular mechanism underlying this event in hepatocellular carcinoma (HCC). Methods Proteasome subunit alpha 5 (PSMA5) expression liver (LIHC) tissues its association with LIHC patients were predicted using StarBase. PSMA5 level human HCC cells was manipulated via transfection. Exosomes isolated from cells, internalized which cocultured cells. Exosome internalization observed after fluorescence labeling. cell migration invasion evaluated by wound healing Transwell assays. Xenograft assay performed investigate role vitro tumorigenesis. assessed enzyme‐linked immunosorbent assay, quantitative reverse transcription polymerase chain reaction, immunohistochemistry. exosomes Janus Kinase 2 (JAK2)/signal transducer activator 3 (STAT3) activation tumors detected Western blot analysis. Results High associated compromised survival patients. knockdown inhibited invasion. downregulated these cell‐isolated successfully facilitated JAK2/STAT3 pathway activation. cell‐secreted exosomal exosome‐induced on attenuated promotion induced exosome‐treated migration/invasion tumorigenesis along vivo Conclusion hinders suppress progression restraining signaling.

Язык: Английский

Autophagy and cancer drug resistance in dialogue: Pre-clinical and clinical evidence DOI
Yi Qin, Milad Ashrafizadeh, Vera Mongiardini

и другие.

Cancer Letters, Год журнала: 2023, Номер 570, С. 216307 - 216307

Опубликована: Июль 12, 2023

Язык: Английский

Процитировано

153
Control of tumor-associated macrophage responses by nutrient acquisition and metabolism DOI Creative Commons
Xian Zhang, Liangliang Ji, Ming O. Li

и другие.

Immunity, Год журнала: 2023, Номер 56(1), С. 14 - 31

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

66
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma DOI
Alessandra De Leo, Alessio Ugolini, Xiaoqing Yu

и другие.

Immunity, Год журнала: 2024, Номер 57(5), С. 1105 - 1123.e8

Опубликована: Май 1, 2024

Язык: Английский

Процитировано

59
OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy DOI
Yongkang Yu, Tingxuan Li,

Meitong Ou

и другие.

Journal of Controlled Release, Год журнала: 2023, Номер 365, С. 469 - 479

Опубликована: Дек. 2, 2023

Язык: Английский

Процитировано

55
Targeting USP8 Inhibits O‐GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT DOI Creative Commons
Jianing Tang,

Guo Long,

Kuan Hu

и другие.

Advanced Science, Год журнала: 2023, Номер 10(33)

Опубликована: Окт. 22, 2023

Hepatocellular carcinoma (HCC) is a lethal and aggressive human malignancy. The present study examins the anti-tumor effects of deubiquitylating enzymes (DUB) inhibitors in HCC. It found that inhibitor ubiquitin specific peptidase 8 (USP8) DUB-IN-3 shows most effective anti-cancer responses. Targeting USP8 inhibits proliferation HCC induces cell ferroptosis. In vivo xenograft metastasis experiments indicate inhibition suppresses tumor growth lung metastasis. treatment or depletion decrease intracellular cystine levels glutathione biosynthesis while increasing accumulation reactive oxygen species (ROS). Mechanistical studies reveal stabilizes O-GlcNAc transferase (OGT) via inhibiting K48-specific poly-ubiquitination process on OGT protein at K117 site, STE20-like kinase (SLK)-mediated S716 phosphorylation required for interaction with OGT. Most importantly, O-GlcNAcylates solute carrier family 7, member 11 (SLC7A11) Ser26 cells, which essential SLC7A11 to import from extracellular environment. Collectively, this demonstrates pharmacological knockout can inhibit progression induce ferroptosis decreasing stability OGT, imposes great challenge targeting potential approach treatment.

Язык: Английский

Процитировано

44
Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives DOI Creative Commons

Xiaoli Shi,

Xinyi Wang, Wentao Yao

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 2, 2024

Abstract Metastasis remains a pivotal characteristic of cancer and is the primary contributor to cancer-associated mortality. Despite its significance, mechanisms governing metastasis are not fully elucidated. Contemporary findings in domain biology have shed light on molecular aspects this intricate process. Tumor cells undergoing invasion engage with other cellular entities proteins en route their destination. Insights into these engagements enhanced our comprehension principles directing movement adaptability metastatic cells. The tumor microenvironment plays role facilitating proliferation by enabling navigate through stromal barriers. Such attributes influenced genetic epigenetic changes occurring surrounding milieu. A profound understanding process’s biological indispensable for devising efficacious therapeutic strategies. This review delves recent developments concerning metastasis-associated genes, important signaling pathways, microenvironment, metabolic processes, peripheral immunity, mechanical forces metastasis. In addition, we combine advances particular emphasis prospect developing effective interventions including most popular immunotherapies nanotechnology combat We also identified limitations current research metastasis, encompassing drug resistance, restricted animal models, inadequate biomarkers early detection methods, as well heterogeneity among others. It anticipated that comprehensive will significantly contribute advancement research.

Язык: Английский

Процитировано

33
Metabolic regulation of the immune system in health and diseases: mechanisms and interventions DOI Creative Commons
Tengyue Hu, Changhai Liu, Min Lei

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Окт. 9, 2024

Metabolism, including glycolysis, oxidative phosphorylation, fatty acid oxidation, and other metabolic pathways, impacts the phenotypes functions of immune cells. The regulation system is important in pathogenesis progression numerous diseases, such as cancers, autoimmune diseases diseases. concept immunometabolism was introduced over a decade ago to elucidate intricate interplay between metabolism immunity. definition has expanded from chronic low-grade inflammation reprogramming cells various With being proposed developed, can be gradually summarized becomes more clearer. In context many cancer, disease, occurs inducing proinflammatory or anti-inflammatory effects. phenotypic functional changes caused by further affect development Based on experimental results, targeting cellular promising therapy. this review, we focus introduce their pathways reprogramming, summarize how these effects We thoroughly explore targets treatments based existing studies. challenges translating results into clinical applications field are also summarized. believe that better understanding health will improve management most

Язык: Английский

Процитировано

29
Pan‐Cancer Single‐Cell and Spatial‐Resolved Profiling Reveals the Immunosuppressive Role of APOE+ Macrophages in Immune Checkpoint Inhibitor Therapy DOI Creative Commons
Chuan Liu, Jindong Xie, Bo Lin

и другие.

Advanced Science, Год журнала: 2024, Номер 11(23)

Опубликована: Апрель 3, 2024

Abstract The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore impact APOE + on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. scRNA‐seq bulk RNA‐seq data are Integrated construct an M.Sig model for predicting based distinct molecular signatures macrophage algorithms. Comprehensive analysis as well in vivo vitro experiments applied potential mechanisms affecting response. shows clear advantages efficacy prognosis pan‐cancer patients. proportion is higher non‐responders triple‐negative breast cancer compared with responders, interaction longer distance between CD8 exhausted T (Tex) cells confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, combined treatment best efficacy. real‐world immunotherapy accurately predicts pan‐cancer, which may be associated Tex cells.

Язык: Английский

Процитировано

23
Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities DOI Creative Commons

Yujing Qian,

Yujia Yin,

Xiaocui Zheng

и другие.

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Янв. 7, 2024

Abstract Tumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription but also external signals from the tumor microenvironment (TME), inflammatory metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit spectrum of activities ranging pro-tumorigenic anti-tumorigenic, closely associated with progression clinical prognosis. This review implicates diversity phenotypes functions, how this heterogeneity been re-evaluated advent single-cell technologies, impact TME on TAMs. We current therapies targeting metabolism offer new insights for TAM-dependent anti-tumor immunotherapy focusing critical role different programs

Язык: Английский

Процитировано

21
The effects of metabolism on the immune microenvironment in colorectal cancer DOI Creative Commons

Xingzhao Chen,

Zhiyuan Ma, Zhiqiang Yi

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Март 7, 2024

Abstract Colorectal cancer (CRC) is a malignancy that widely prevalent worldwide. Due to its unsatisfactory treatment outcome and extremely poor prognosis, many studies on the molecular mechanisms pathological of CRC have been published in recent years. The tumor microenvironment (TME) an important feature tumorigenesis one hallmarks development. Metabolic reprogramming currently hot topic research, this provided insights into In particular, metabolic causes changes composition energy nutrients TME. Furthermore, it can alter complex crosstalk between immune cells associated factors, such as macrophages T cells, which play roles TME, turn affecting escape tumors by altering surveillance. review, we summarize several metabolism-related processes tumors. Our results showed regulated influences development CRC.

Язык: Английский

Процитировано

20