The Role of TIM-3 in Glioblastoma Progression DOI Creative Commons

Farah Ahmady,

Amit Sharma, Adrian Achuthan

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 346 - 346

Published: Feb. 27, 2025

Several immunoregulatory or immune checkpoint receptors including T cell immunoglobulin and mucin domain 3 (TIM-3) have been implicated in glioblastoma progression. Rigorous investigation over the last decade has elucidated TIM-3 as a key player inhibiting activation several associated molecules identified both upstream downstream that mediate dysfunction mechanistically. However, despite reviews being published on other such PD-1 CTLA-4 setting, no extensive review exists specifically focuses role of progression immunosuppression. Here, we critically summarize current literature regarding expression prognostic marker for glioblastoma, its profile cells patients exploration anti-TIM-3 agents pre-clinical models potential clinical application.

Language: Английский

The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets DOI Creative Commons
Jiangbin Ren,

Bangjie Xu,

Jianghao Ren

et al.

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(9), P. 1269 - 1269

Published: Aug. 31, 2023

Glioma is the most common and malignant tumor of central nervous system. Glioblastoma (GBM) aggressive glioma, with a poor prognosis no effective treatment because its high invasiveness, metabolic rate, heterogeneity. The microenvironment (TME) contains many tumor-associated macrophages (TAMs), which play critical role in proliferation, invasion, metastasis, angiogenesis indirectly promote an immunosuppressive microenvironment. TAM divided into tumor-suppressive M1-like (classic activation macrophages) tumor-supportive M2-like (alternatively activated polarized cells. TAMs exhibit phenotype initial stages progression, along promotion lysing tumors functions T cells NK cells, growth suppressed, they rapidly transform macrophages, progression. In this review, we discuss mechanism by M1- M2-polarized or inhibit glioblastoma indicate future directions for treatment.

Language: Английский

Citations

22
Tumor-associated monocytes promote mesenchymal transformation through EGFR signaling in glioma DOI Creative Commons
Yiyun Chen, Ran Huo, Weirong Kang

et al.

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(9), P. 101177 - 101177

Published: Aug. 30, 2023

The role of brain immune compartments in glioma evolution remains elusive. We profile cells microenvironment and the matched peripheral blood from 11 patients. Glioblastoma exhibits specific infiltration blood-originated monocytes expressing epidermal growth factor receptor (EGFR) ligands EREG AREG, coined as tumor-associated (TAMo). TAMo is mutually exclusive with EGFR alterations (p = 0.019), while co-occurring mesenchymal subtype 4.7 × 10−7) marking worse prognosis 0.004 0.032 two cohorts). Evolutionary analysis initial-recurrent pairs single-cell study a multi-centric glioblastoma reveal association between elevated transformation. Further analyses identify FOSL2 master regulator demonstrates that FOSL2-EREG/AREG-EGFR signaling axis promotes invasion vitro. Collectively, we tumor its driving activating to shape evolution.

Language: Английский

Citations

19
An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype DOI Open Access
Yaochuan Zhang, Yifu Song, Xiaoliang Wang

et al.

Cancer Immunology Research, Journal Year: 2024, Volume and Issue: 12(3), P. 363 - 376

Published: Jan. 30, 2024

Abstract Extensive infiltration by tumor-associated macrophages (TAM) in combination with myeloid-derived suppressor cells constitute the immunosuppressive microenvironment and promote malignant phenotype of gliomas. The aggressive mesenchymal (MES)-subtype glioma stem (GSC) are prominent However, underlying immune-suppressive mechanisms still unknown. current study showed that antitumor immune was activated Nfat1−/− mice, suggesting induction nuclear factor T cells-1 (NFAT1). In TAMs, NFAT1 could upregulate transcriptional activity complement 3 (C3) increase secretion C3a, which then bind to C3aR M2-like macrophage polarization activating TIM-3. Simultaneously, C3a/C3aR Ca2+-NFAT1 pathway, forming a positive feedback loop for further promoted MES transition GSCs. Finally, disruption this using inhibitor significantly inhibited growth both vitro vivo. demonstrated NFAT1-C3a-C3aR induces TAMs promotes GSCs, might be potential therapeutic target glioma.

Language: Английский

Citations

8
Implantable Microneedle‐Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse DOI Open Access
Yulin Zhang, Z Fang,

Zejuan Liu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2–3 cm) of the initial resected lesion due to unreachable residual cancerous cells. Here, completely biodegradable microneedle for cavity delivery glioblastoma‐associated macrophages (GAMs)‐activating immune nano‐stimulator that mitigates glioblastoma is reported. The tumor lesion‐directed biocompatible releases and toll‐like receptor 9 agonist in controlled manner until microneedles degrade over 1 week, efferently induce situ phonotypic shifting GAMs from anti‐ pro‐inflammatory recurrence obviously inhibited. implantable offer significant improvement conventional transdermal ones, as they are 100% degradable, ensuring safe application cavities. It also revealed T cells recruited niche initiate anti‐tumor response eradicate Taken together, this work provides potential strategy immunomodulating postoperative mitigate patients, which may have broad applications other malignancies intervention.

Language: Английский

Citations

8
Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3/Galectin-9 pathway DOI Creative Commons
Qiqi Zhu,

Yiming Yang,

Kexin Chen

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 18, 2024

Abstract Background Overexpression of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is related to the exhaustion CD8 + tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL). However, mechanism TIM3-mediated TILs DLBCL remains poorly understood. Therefore, we aimed clarify potential pathway involved its significance DLBCL. Methods The expression TIM3 correlation with exhaustion, key ligand TIM3, were analyzed using single-cell RNA sequencing validated by sequencing. biological TIM3-related was investigated based on sequencing, immunohistochemistry, reverse transcription-quantitative polymerase chain reaction data. Finally, possible regulatory explored Results Our results demonstrated that TILs, especially terminally exhausted state, major clusters expressed Galectin-9, mainly M2 macrophages, can induce through TIM3/Galectin-9 pathway. Meanwhile, high enrichment immunosuppressive tumor microenvironment, severe clinical manifestations, inferior prognosis, poor response CHOP-based chemotherapy, predict efficacy immune checkpoint blockade therapy Furthermore, may be regulated IFN-γ signaling Conclusions study highlights plays a crucial role escape DLBCL, which facilitates further functional studies could provide theoretical basis for development novel immunotherapy

Language: Английский

Citations

7
The role of Tim-3 blockade in the tumor immune microenvironment beyond T cells DOI Creative Commons
Jie Zhang, Longsheng Wang, Hongjie Guo

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 209, P. 107458 - 107458

Published: Oct. 11, 2024

Numerous preclinical studies have demonstrated the inhibitory function of T cell immunoglobulin mucin domain-containing protein 3 (Tim-3) on cells as an receptor, leading to clinical development anti-Tim-3 blocking antibodies. However, recent shown that Tim-3 is expressed not only but also multiple types in tumor microenvironment (TME), including dendritic (DCs), natural killer (NK) cells, macrophages, and cells. Therefore, blockade immune affect influence functions other For example, can enhance ability DCs regulate innate adaptive immunity. The role NK controversial, it antitumor under certain conditions while having opposite effect situations. Additionally, promote reversal macrophage polarization from M2 phenotype M1 phenotype. Furthermore, inhibit by suppressing proliferation metastasis In summary, increasing evidence has plays a critical efficacy therapy. Understanding therapy non-T help elucidate diverse responses observed patients, better relevant therapeutic strategies. This review aims discuss TME emphasize impact beyond

Language: Английский

Citations

6
GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway DOI
Hai-Di Li, Xin Chen, Jiejie Xu

et al.

Hepatology, Journal Year: 2023, Volume and Issue: 79(2), P. 392 - 408

Published: July 5, 2023

Background and Aims: The common characteristics of alcohol-associated liver injury (ALI) include abnormal function, infiltration inflammatory cells, generation oxidative stress. gastrin-releasing peptide receptor (GRPR) is activated by its neuropeptide ligand, (GRP). GRP/GRPR appears to induce the production cytokines in immune cells promotes neutrophil migration. However, effects ALI are unknown. Approach Results: We found high GRPR expression patients with steatohepatitis increased pro-GRP levels peripheral blood mononuclear these compared that control. Increased GRP may be associated histone H3 lysine 27 acetylation induced alcohol, which then binding. Grpr -/- flox/flox LysM Cre mice alleviated ethanol-induced relieved steatosis, lower serum alanine aminotransferase, aspartate triglycerides, malondialdehyde, superoxide dismutase levels, reduced influx, decreased release chemokines. Conversely, overexpression showed opposite effects. pro-inflammatory stress roles might dependent on IRF1-mediated Caspase-1 inflammasome NOX2-dependent reactive oxygen species pathway, respectively. In addition, we verified therapeutic preventive RH-1402, a novel antagonist, for ALI. Conclusions: A knockout or antagonist during excess alcohol intake could have anti-inflammatory antioxidative roles, as well provide platform modification-based therapy

Language: Английский

Citations

13
Glioblastoma stem cell-derived exosomal miR-374b-3p promotes tumor angiogenesis and progression through inducing M2 macrophages polarization DOI Creative Commons

Shilu Huang,

Peng Zhang,

Nanheng Yin

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(3), P. 109270 - 109270

Published: Feb. 22, 2024

Glioblastoma stem cells (GSCs) reside in hypoxic periarteriolar niches of glioblastoma micro-environment, however, the crosstalk GSCs with macrophages on regulating tumor angiogenesis and progression are not fully elucidated. GSCs-derived exosomes (GSCs-exos) essential mediators during immune-microenvironment remodeling initiated by GSCs, resulting M2 polarization tumor-associated (TAMs) as we reported previously. Our data disclosed aberrant upregulation miR-374b-3p both clinical specimens human cell lines GSCs. MiR-374b-3p level was high GSCs-exos can be internalized macrophages. Mechanistically, exosomal induced downregulating phosphatase tensin expression, thereby promoting migration tube formation vascular endothelial after coculture Cumulatively, these indicated that enhance inducing macrophages, well promote malignant glioblastoma. Targeting may serve a potential target against

Language: Английский

Citations

5
Targeting MS4A4A: A novel pathway to improve immunotherapy responses in glioblastoma DOI Creative Commons

Guangcai Shao,

Xiangguo Cui,

Yiliang Wang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(7)

Published: July 1, 2024

Abstract Introduction Glioblastoma (GBM) remains a challenging brain tumor to treat, with limited response PD‐1 immunotherapy due tumor‐associated macrophages (TAMs), specifically the M2 phenotype. This study explores potential of MS4A4A (membrane spanning four domains, subfamily A, member 4A) inhibition in driving macrophage polarization toward M1 phenotype via ferroptosis pathway enhance effectiveness GBM. Methods Single‐cell RNA sequencing and spatial transcriptomic analyses were employed characterize expression In vitro studies utilizing TAM cultures, flow cytometry, western blot validations conducted assess impact on immune microenvironment polarization. vivo models, including subcutaneous orthotopic transplantation mice, utilized evaluate effects knockout combined checkpoint blockade (ICB) therapy growth immunotherapy. Results Distinct subsets GBM‐associated identified, distribution tissue elucidated. experiments demonstrated that inhibiting combining ICB effectively inhibited growth, reshaped by reducing infiltration enhancing CD8 + T‐cell infiltration, ultimately leading complete eradication. Conclusion shows promise converting ferroptosis, decreasing M2‐TAM GBM These findings offer novel approach developing more effective immunotherapeutic strategies for

Language: Английский

Citations

5
Galectin functions in cancer-associated inflammation and thrombosis DOI Creative Commons

Linus Kruk,

Attila Braun, Érika Cosset

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Feb. 17, 2023

Galectins are carbohydrate-binding proteins that regulate many cellular functions including proliferation, adhesion, migration, and phagocytosis. Increasing experimental clinical evidence indicates galectins influence steps of cancer development by inducing the recruitment immune cells to inflammatory sites modulating effector function neutrophils, monocytes, lymphocytes. Recent studies described different isoforms can induce platelet aggregation, granule release through interaction with platelet-specific glycoproteins integrins. Patients and/or deep-venous thrombosis have increased levels in vasculature, suggesting these could be important contributors cancer-associated inflammation thrombosis. In this review, we summarize pathological role thrombotic events, influencing tumor progression metastasis. We also discuss potential anti-cancer therapies targeting context

Language: Английский

Citations

12