Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution DOI Creative Commons
Laura M. Bartos, Sabrina V. Kirchleitner, Zeynep Ilgin Kolabas

и другие.

Science Advances, Год журнала: 2023, Номер 9(43)

Опубликована: Окт. 27, 2023

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach immunomagnetic cell sorting after vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect allocation PET signals TME. In mice implanted glioblastoma, translocator protein (TSPO) uptake per was higher compared tumor-associated microglia/macrophages (TAMs), validated by levels. Translation vitro scRadiotracing patients glioma immediately resection confirmed single-cell TSPO tracer cells immune cells. Across species, explained heterogeneity individual TSPO-PET signals. consideration and type abundance, were main contributor enrichment glioblastoma; however, proteomics identified potential targets highly specific for TAMs. Combining measures 3D facilitates precise serves validate emerging novel TAM-specific radioligands.

Язык: Английский

Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways DOI Creative Commons

Yunji Yan,

Shengwei Bai,

Hongxi Han

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 15, 2024

Abstract Background In the tumor immune microenvironment (TIME), triggering receptor expressed on myeloid cells 2 (trem2) is widely considered to be a crucial molecule tumor-associated macrophages(TAMs). Multiple studies have shown that trem2 may function as an checkpoint in various malignant tumors, mediating evasion. However, its specific molecular mechanisms, especially glioma, remain elusive. Methods Lentivirus was transfected establish with stable knockdown of trem2. A Transwell system used for segregated coculture glioma and microglia. Western blotting, quantitative real-time polymerase chain reaction (qRT‒PCR), immunofluorescence (IF) were measure expression levels target proteins. The proliferation, invasion, migration detected by colony formation, cell counting kit-8 (CCK8), 5-ethynyl-2’-deoxyuridine (EdU) transwell assays. cycle, apoptosis rate reactive oxygen species (ROS) level assessed using flow cytometry comet assay tube formation detect DNA damage angiogenesis activity, respectively. Gl261 lines C57BL/6 mice construct orthotopic transplantation model. Results Trem2 highly overexpressed TAMs. Knocking down microglia suppressed growth activity vivo vitro. Mechanistically, promoted proinflammatory inhibited anti-inflammatory activating jak2/stat1 inhibiting NF-κB p50 signaling pathway. produced high concentrations nitric oxide (NO) cytokines TNF-α, IL-6, IL-1β, caused further cells. Conclusions Our findings revealed plays significant role TIME gliomas. Knockdown might help improve efficiency delaying progression provide new ideas treatment glioma.

Язык: Английский

Процитировано

7
Deciphering microglia phenotypes in health and disease DOI Creative Commons
Christopher Balak, Claudia Z. Han, Christopher K. Glass

и другие.

Current Opinion in Genetics & Development, Год журнала: 2024, Номер 84, С. 102146 - 102146

Опубликована: Янв. 3, 2024

Microglia are the major immune cells of central nervous system (CNS) that perform numerous adaptive functions required for normal CNS development and homeostasis but also linked to neurodegenerative behavioral diseases. function strongly influenced by brain environmental signals integrated at level transcriptional enhancers drive specific programs gene expression. Here, we describe a conceptual framework how lineage-determining signal-dependent transcription factors interact select regulate ensembles determine microglia function. We then highlight recent findings advance these concepts conclude with consideration open questions represent some hurdles be addressed in future.

Язык: Английский

Процитировано

6
TREM2 promotes glioma progression and angiogenesis mediated by microglia/brain macrophages DOI Creative Commons
Xuezhen Chen, Yue Zhao, Yimin Huang

и другие.

Glia, Год журнала: 2023, Номер 71(11), С. 2679 - 2695

Опубликована: Авг. 28, 2023

Triggering receptor expressed on myeloid cell 2 (TREM2), a cell-specific signaling molecule, controls essential functions of microglia and impacts the pathogenesis Alzheimer's disease other neurodegenerative disorders. TREM2 is also highly in tumor-associated macrophages different types cancer. Here, we studied whether influences glioma progression. We found gender-dependent effect growth wild-type (WT) animals injected with GL261-EGFP cells. Most importantly, promotes progression male but not female animals. The accumulation glioma-associated microglia/macrophages (GAMs) CD31+ blood vessel density reduced TREM2-deficient mice. A transcriptomic analysis tissue revealed that deficiency suppresses immune-related genes. In an organotypic slice model devoid functional vascularization immune components from periphery, tumor size was affected by TREM2-deficiency. human resection samples glioblastoma, upregulated GAMs. Based Cancer Genome Atlas Program (TCGA) Chinese Glioma (CGGA) databases, expression levels were negatively correlated survival. Thus, TREM2-dependent crosstalk between GAMs vasculature formation growth.

Язык: Английский

Процитировано

14
TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas DOI
Jiaying Zheng, Lingxiao Wang, Shunyi Zhao

и другие.

Neuro-Oncology, Год журнала: 2023, Номер 26(5), С. 811 - 825

Опубликована: Ноя. 6, 2023

Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated promoting progression immunosuppression. Modulating response myeloid has emerged as a promising new approach for cancer treatment. In this regard, we focus on Triggering Receptor Expressed Cells 2 (TREM2), which recently novel immune modulator peripheral tumors.

Язык: Английский

Процитировано

12
Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth DOI Creative Commons
Alberto Rivera-Ramos, Luis Cruz-Hernández, Rocío Talaverón

и другие.

Cancer Letters, Год журнала: 2024, Номер 591, С. 216879 - 216879

Опубликована: Апрель 16, 2024

Galectin-3 (Gal-3) is a multifunctional protein that plays pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although involvement Gal-3 tumour progression, resistance to treatment immunosuppression has long been studied different cancer types, mainly outside system, its elevated expression myeloid glial cells underscores profound impact on brain's immune response. In this context, microglia infiltrating macrophages, predominant non-cancerous within microenvironment, play critical roles establishing an immunosuppressive milieu diverse brain tumours. Through utilisation primary cell cultures immortalised microglial lines, we have elucidated promoting migration, invasion, phenotypic activation. Furthermore, employing two distinct vivo models encompassing (glioblastoma) secondary tumours (breast metastasis), our histological transcriptomic analysis show depletion triggers robust pro-inflammatory response notably based interferon-related pathways. Interestingly, prominently observed tumour-associated macrophages (TAMs), resulting suppression growth.

Язык: Английский

Процитировано

4
Mechanisms of TREM2 mediated immunosuppression and regulation of cancer progression DOI Creative Commons
Lei Xia,

Ya Ni Gou,

Jin Yong Hao

и другие.

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Апрель 25, 2024

Cancer immunotherapy has recently emerged as a key strategy for cancer treatment. TREM2, target regulating the tumor immune microenvironment, is important in treatment and progression. TREM2 an signaling hub that regulates multiple pathological pathways. It not only suppresses anti-tumor responses by inhibiting T cell-mediated responses, but it also influences tumorigenesis affecting NK immunity. Noticeably, expression levels vary significantly among different cells, can regulate progression modulating various Above all, summarizing role of mechanism which progression, this paper clarifies TREM2’s both therapy, identifying new therapeutic oncology diseases.

Язык: Английский

Процитировано

4
Autophagy in glioblastoma: A mechanistic perspective DOI

Durgesh Meena,

Sushmita Jha

International Journal of Cancer, Год журнала: 2024, Номер 155(4), С. 605 - 617

Опубликована: Май 8, 2024

Abstract Glioblastoma (GBM) is one of the most lethal malignancies in humans. Even after surgical resection and aggressive radio‐ or chemotherapies, patients with GBM can survive for less than 14 months. Extreme inter‐tumor intra‐tumor heterogeneity poses a challenge resolving recalcitrant pathophysiology. tumor microenvironment (TME) exhibits diverse cellular composition processes contributing to progression therapeutic resistance. Autophagy such process; that demonstrates cell‐specific TME context‐dependent role progression, leading either promotion suppression progression. regulate cell function directly via regulation survival, migration, invasion, indirectly by affecting as immune population, metabolism, glioma stem cells. This review comprehensively investigates autophagy

Язык: Английский

Процитировано

4
Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications DOI Creative Commons

Chuncha Bao,

Qing Ma, Xuchao Ying

и другие.

EBioMedicine, Год журнала: 2024, Номер 111, С. 105502 - 105502

Опубликована: Дек. 10, 2024

Язык: Английский

Процитировано

4
Targeting immune checkpoints on myeloid cells: current status and future directions DOI Creative Commons

Chuhan Ma,

Yang Li, Min Li

и другие.

Cancer Immunology Immunotherapy, Год журнала: 2025, Номер 74(2)

Опубликована: Янв. 3, 2025

Myeloid cells accumulate extensively in most tumors and play a critical role immunosuppression of the tumor microenvironment (TME). Like T cells, myeloid also express immune checkpoint molecules, which induce immunosuppressive phenotype these cells. In this review, we summarize tumor-promoting function expression four types cells: macrophages, neutrophils, dendritic myeloid-derived suppressor are main components TME. By summarizing research status checkpoints, propose that blocking checkpoints on might be an effective strategy to reverse Moreover, combining nanotechnology, cellular therapy, bispecific antibodies achieve precise targeting can help avoid adverse effects systemic administration, ultimately achieving balance between efficacy safety cancer therapy.

Язык: Английский

Процитировано

0
A bird’s eye view to the homeostatic, Alzheimer and Glioblastoma attractors DOI Creative Commons
Joan Nieves, Gabriel Gil, Augusto González

и другие.

Heliyon, Год журнала: 2025, Номер 11(4), С. e42445 - e42445

Опубликована: Фев. 1, 2025

Dimensional reduction analysis of available data for white matter the brain allows to locate normal (homeostatic), Glioblastoma and Alzheimer's disease attractors in gene expression space identify paths related transitions like carcinogenesis or onset. A predefined path aging is also apparent, which consistent with hypothesis programmatic aging. In addition, reasonable assumptions about relative strengths allow draw a schematic landscape fitness: Wright's diagram. These simple diagrams reproduce known relations between aging, disease, rise interesting questions possible connection this tissue. We anticipate that similar multiple other tissues could be useful understanding biology apparently unrelated diseases disorders, discovery unexpected clues their treatment.

Язык: Английский

Процитировано

0