VISTA in hematological malignancies: a review of the literature DOI Creative Commons

Yuanjia Duan,

Xiaotong Ren, Xinyu Guo

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 17, 2024

In recent years, tumor immunotherapy has become an active research area, with the emergence of immune checkpoint inhibitors (ICIs) revolutionizing immunotherapy. Clinical evidence indicates that programmed cell death protein 1 (PD-1) monoclonal antibodies and other drugs have remarkable therapeutic effects. V-domain Ig suppressor T-cell activation (VISTA) is a new type receptor highly expressed in various tumors. It co-expressed PD-1, immunoglobulin domain, mucin domain-3 (Tim-3), immunoglobulin, immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) associated prognosis, which suggests it may be target for As no mature drugs, VISTA acute myeloid leukemia (AML), multiple myeloma (MM), hematological malignancies; however, its pathogenic mechanism should defined to better guide treatment.

Language: Английский

Eliminating a barrier: Aiming at VISTA, reversing MDSC-mediated T cell suppression in the tumor microenvironment DOI Creative Commons

Yayuan Deng,

Mengjia Shi,

Yi Lin

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(17), P. e37060 - e37060

Published: Aug. 30, 2024

Language: Английский

Citations

31
LRIG1 engages ligand VISTA and impairs tumor-specific CD8 + T cell responses DOI
Hieu Minh Ta, Dia Roy, Keman Zhang

et al.

Science Immunology, Journal Year: 2024, Volume and Issue: 9(95)

Published: May 17, 2024

Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor T cell activation (VISTA) an immune target; however, downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats immunoglobulin-like domains 1 (LRIG1) as VISTA binding partner, which acts inhibitory receptor by engaging suppressing pathways. Mice cell-specific LRIG1 deletion developed superior responses because expansion tumor-specific cytotoxic lymphocytes (CTLs) increased effector function survival. Sustained tumor control was associated reduction quiescent CTLs (TCF1

Language: Английский

Citations

14
VISTA-induced tumor suppression by a four amino acid intracellular motif DOI Creative Commons
Yan Zhao,

T Andoh,

Fatima Charles

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

Summary VISTA is a key immune checkpoint receptor under investigation for cancer immunotherapy; however, its signaling mechanisms remain unclear. Here we identify conserved four amino acid (NPGF) intracellular motif in that suppresses cell proliferation by constraining cell-intrinsic growth signaling. The NPGF binds to the adapter protein NUMB and recruits Rab11 endosomal recycling machinery. We characterize class of triple-negative breast cancers with high expression low proliferative index. In tumor cells levels, sequesters at endosomes, which interferes epidermal factor (EGFR) trafficking suppress growth. These effects do not require canonical ligands, nor functioning system. As consequence expression, EGFR remains abnormally phosphorylated cannot propagate ligand-induced Mutation domain reverts VISTA-induced suppression multiple mouse models. results define mechanism represses control malignant epithelial They also distinct residues are critical could be exploited improve immunotherapy.

Language: Английский

Citations

1
Immune-cell signatures of persistent inflammation, immunosuppression, and catabolism syndrome after sepsis DOI Creative Commons

Xingfeng Sun,

Wen-Chen Luo,

Shaoqiang Huang

et al.

Med, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Management of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) after sepsis remains challenging for patients in the intensive care unit, experiencing poor quality life death. However, immune-cell signatures with PICS remain unclear. We determined at single-cell resolution. Murine cecal ligation puncture models were applied validation. Immune functions two enriched monocyte subpopulations, Mono1 Mono4, suppressed substantially partially restored exhibited immunosuppressive pro-apoptotic effects on B CD8T cells. Patients had reduced naive memory cells proliferated plasma Besides, showed an active antigen processing presentation gene signature compared to those sepsis. better prognoses more IGHA1-plasma CD8TEMRA displayed signs proliferation immune dysfunction PICS-death group contrast PICS-alive group. Megakaryocytes was pronounced than healthy controls, notable changes anti-inflammatory immunomodulatory observed verified mice models. Our study evaluated level, identifying heterogeneity present within subsets, facilitating prediction disease progression development effective intervention. This work supported by National Natural Science Foundation China, Shanghai Municipal Health Commission "Yiyuan New Star" Youth Medical Talent Cultivating Program, Clinical Research Center Anesthesiology.

Language: Английский

Citations

1
Polyamine metabolism and anti-tumor immunity DOI Creative Commons
Jingyi Wu, Yan Zeng,

Yu-Yang You

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 18, 2025

Growing attention has been directed toward the critical role of polyamines in tumor microenvironment and immune regulation. Polyamines, primarily comprising putrescine, spermidine, spermine, are tightly regulated through coordinated biosynthesis, catabolism, transport, with distinct metabolic patterns between normal cancerous tissues. Emerging evidence highlights pivotal polyamine metabolism initiation, progression, metastasis. This review aims to elucidate differences catabolism tissues, as well associated alterations epigenetic modifications resistance checkpoint blockade driven by metabolism. Polyamine influences both cells modulating cell phenotypes-shifting them towards either suppression or evasion within microenvironment. Additionally, impacts immunotherapy its regulation key enzymes. also explores potential therapeutic targets summarizes roles inhibitors combination for cancer treatment, offering a novel perspective on strategies.

Language: Английский

Citations

1
The roles of arginases and arginine in immunity DOI
Stefania Canè, Roger Geiger, Vincenzo Bronte

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Language: Английский

Citations

6
FOXO1 pathway activation by VISTA immune checkpoint restrains pulmonary ILC2 functions DOI Creative Commons
Mohammad Hossein Kazemi,

Zahra Momeni-Varposhti,

X. Li

et al.

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Type-2 innate lymphoid cells (ILC2s) play a pivotal role in the development of airway hyperreactivity (AHR). However, regulatory mechanisms governing ILC2 function remain inadequately explored. This study uncovers V-domain Ig suppressor T cell activation (VISTA) as an inhibitory immune checkpoint crucial for modulating ILC2-driven lung inflammation. VISTA is upregulated activated pulmonary ILC2s and plays key regulating inflammation, VISTA-deficient demonstrate increased proliferation function, resulting elevated type-2 cytokine production exacerbation AHR. Mechanistically, stimulation activates Forkhead box O1 (FOXO1), leading to modulation function. The suppressive effects FOXO1 on effector were confirmed using inhibitors activators. Moreover, exhibit enhanced fatty acid oxidation oxidative phosphorylation meet their high energy demands. Therapeutically, agonist treatment reduces both ex vivo vivo, significantly alleviating Our murine findings validated human ILC2s, where humanized mouse model studies unravel regulation via pathway, presenting potential therapeutic strategies allergic asthma by responses.

Language: Английский

Citations

0
Harnessing amino acid pathways to influence myeloid cell function in tumor immunity DOI Creative Commons

Jiongli Pan,

Yi Lin,

Xinyuan Liu

et al.

Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)

Published: Feb. 4, 2025

Abstract Amino acids are pivotal regulators of immune cell metabolism, signaling pathways, and gene expression. In myeloid cells, these processes underlie their functional plasticity, enabling shifts between pro-inflammatory, anti-inflammatory, pro-tumor, anti-tumor activities. Within the tumor microenvironment, amino acid metabolism plays a crucial role in mediating immunosuppressive functions contributing to progression. This review delves into mechanisms by which specific acids—glutamine, serine, arginine, tryptophan—regulate function polarization. Furthermore, we explore therapeutic potential targeting enhance immunity, offering insights novel strategies for cancer treatment.

Language: Английский

Citations

0
Antitumor potential of polyamines in cancer DOI Creative Commons
He Liu, Yi Liu, Xinyue Wang

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

The dysregulation of polyamines in tumors has made polyamine metabolism an appealing target for cancer therapy. Gene mutations drive the reprogramming tumors, presenting promising opportunities clinical treatment. proposed strategies involve inhibiting biosynthesis while also targeting transport system as antitumor approaches. A growing number drugs aimed at and systems are undergoing trials. Polyamine plays a role regulating signaling pathways, suggesting potential combination therapies Furthermore, supplemental substances have demonstrated activity, indicating that combining with downstream targets or immunotherapy could offer significant benefits. These discoveries open new avenues leveraging anticancer

Language: Английский

Citations

0
MiR- 150 deletion promotes lung tumor growth by upregulating P-STAT3 and ROS in MDSCs DOI Creative Commons

Anqi X. Qin,

Hao Chen, Fan Xu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 15, 2025

Language: Английский

Citations

0