Cell Death and Differentiation, Journal Year: 2024, Volume and Issue: 31(6), P. 738 - 752
Published: April 9, 2024
Language: Английский
Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(1)
Published: Jan. 2, 2023
Glioblastoma (GBM) is the most aggressive tumor in central nervous system and contains a highly immunosuppressive microenvironment (TME). Tumor-associated macrophages microglia (TAMs) are dominant population of immune cells GBM TME that contribute to hallmarks, including immunosuppression. The understanding TAMs has been limited by lack powerful tools characterize them. However, recent progress on single-cell technologies offers an opportunity precisely at level identify new TAM subpopulations with specific tumor-modulatory functions GBM. In this Review, we discuss heterogeneity plasticity summarize current TAM-targeted therapeutic potential We anticipate use followed functional studies will accelerate development novel effective therapeutics for patients.
Language: Английский
Citations
187
Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561
Published: April 2, 2023
Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.
Language: Английский
Citations
122
Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)
Published: May 8, 2024
Abstract Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, exploration of emerging modalities such as immunotherapy integration medicine engineering technology therapy, efficacy these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny inhibitory milieu within GBM has underscored significance cellular constituents microenvironment their interactions with cells neurons. Novel immune targeted therapy strategies have emerged, offering promising avenues for advancing treatment. One pivotal mechanism orchestrating immunosuppression involves aggregation myeloid-derived suppressor (MDSCs), glioma-associated macrophage/microglia (GAM), regulatory T (Tregs). Among these, MDSCs, though constituting minority (4–8%) CD45 + GBM, play central component fostering evasion propelling tumor progression, angiogenesis, invasion, metastasis. MDSCs deploy intricate mechanisms that adapt dynamic (TME). Understanding interplay between provides compelling basis This review seeks elucidate inherent explore existing targets, consolidate insights into MDSC induction contribution immunosuppression. Additionally, comprehensively surveys ongoing clinical trials potential strategies, envisioning future where targeting could reshape landscape GBM. Through synergistic other modalities, this approach can establish multidisciplinary, multi-target paradigm, ultimately improving prognosis quality life patients
Language: Английский
Citations
62
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: March 25, 2024
Abstract The innate immune pathway is receiving increasing attention in cancer therapy. This ubiquitous across various cell types, not only cells but also adaptive cells, tumor and stromal cells. Agonists targeting the have shown profound changes microenvironment (TME) improved prognosis preclinical studies. However, to date, clinical success of drugs remains limited. Interestingly, recent studies that activation can paradoxically promote progression. uncertainty surrounding therapeutic effectiveness targeted for a critical issue needs immediate investigation. In this review, we observe role demonstrates heterogeneity, linked development stage, status, specific types. We propose within TME, exhibits multidimensional diversity. diversity fundamentally rooted cellular heterogeneity manifested as variety signaling networks. pro-tumor effect essentially reflects suppression classical pathways potential alternative pathways. Refining our understanding tumor’s network employing appropriate strategies enhance ability harness anti-tumor ultimately bridge gap from application.
Language: Английский
Citations
54
Cell Reports, Journal Year: 2023, Volume and Issue: 42(2), P. 112127 - 112127
Published: Feb. 1, 2023
Glioblastoma (GBM) is one of the most aggressive tumors in adult central nervous system. We previously revealed that circadian regulation glioma stem cells (GSCs) affects GBM hallmarks immunosuppression and GSC maintenance a paracrine autocrine manner. Here, we expand mechanism involved angiogenesis, another critical hallmark, as potential basis underlying CLOCK's pro-tumor effect GBM. Mechanistically, CLOCK-directed olfactomedin like 3 (OLFML3) expression results hypoxia-inducible factor 1-alpha (HIF1α)-mediated transcriptional upregulation periostin (POSTN). As result, secreted POSTN promotes tumor angiogenesis via activation TANK-binding kinase 1 (TBK1) signaling endothelial cells. In mouse patient-derived xenograft models, blockade POSTN-TBK1 axis inhibits progression angiogenesis. Thus, CLOCK-POSTN-TBK1 circuit coordinates key tumor-endothelial cell interaction represents an actionable therapeutic target for
Language: Английский
Citations
46
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 5, 2024
Abstract Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs migration lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling functional studies demonstrate A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer activator transcription 3 (STAT3) transcriptional co-activators in cells to upregulate C-C motif chemokine ligand 2 (CCL2) CCL7, which recruit macrophages into microenvironment. Reciprocally, infiltrating produce LDHA-containing vesicles promote glycolysis, proliferation, survival. Genetic pharmacological inhibition LDHA-mediated tumor-macrophage symbiosis markedly suppresses progression mouse models. Analysis plasma samples patients confirms LDHA its downstream signals potential biomarkers correlating positively with density. Thus, provides therapeutic targets for
Language: Английский
Citations
39
Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1354 - 1375
Published: Oct. 15, 2024
Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard care offers minimal clinical benefit, most GBM patients experience recurrence after treatment. In recent years, significant advancements have been made the development novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance many advanced cancers. However, benefit immune-based treatments limited because unique immune profiles, cell heterogeneity, immunosuppressive microenvironment. this review, we present a detailed overview current immunotherapeutic discuss challenges potential molecular mechanisms underlying GBM. Furthermore, provide in-depth discussion regarding GBM, which will likely require combination therapies.
Language: Английский
Citations
22
Nature Cancer, Journal Year: 2024, Volume and Issue: 5(4), P. 546 - 556
Published: April 23, 2024
Language: Английский
Citations
19
Burns & Trauma, Journal Year: 2025, Volume and Issue: 13
Published: Jan. 1, 2025
The circadian clock is an internal timekeeper system that regulates biological processes through a central and peripheral clocks controlling various genes. Basic helix-loop-helix ARNT-like 1 (BMAL1), also known as aryl hydrocarbon receptor nuclear translocator-like protein (ARNTL1), key component of the clock. deletion BMAL1 alone can abolish rhythms human body. plays critical role in immune cell function. Dysregulation linked to immune-related diseases such autoimmune diseases, infectious cancer, vice versa. This review highlights significant governing cells, including their development, differentiation, migration, homing, metabolism, effector functions. study explores how dysregulation have far-reaching implications potentially contribute onset sepsis, trauma. Furthermore, this discusses treatments for target disorders. Understanding impact on function provide insights into pathogenesis help development more effective treatment strategies. Targeting has been demonstrated achieve good efficacy indicating its promising potential targetable therapeutic these diseases.
Language: Английский
Citations
4
Research, Journal Year: 2025, Volume and Issue: 8
Published: Jan. 1, 2025
The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis cancer progression. Aging well-established primary risk for while disruptions rhythms are intricately associated with progression of various tumors. Moreover, itself disrupts leading to physiological changes that may accelerate development. Despite these connections, specific interplay processes their collective impact on remains inadequately explored literature. In this review, we systematically explore influence We discuss how core genes tumor prognosis, highlighting shared hallmarks such genomic instability, cellular senescence, chronic inflammation. Furthermore, examine aging, focusing crosstalk contributes tumorigenesis, proliferation, apoptosis, well metabolism stability. By elucidating common pathways linking review provides new insights into pathophysiology identifies potential therapeutic strategies. propose targeting regulation could pave way novel treatments, including chronotherapy antiaging interventions, which offer important benefits clinical management cancer.
Language: Английский
Citations
2