A pan-cancer analysis of the biological function and clinical value of BTLA in tumors DOI Open Access

Xianglai Jiang,

Jing He,

YONGFENG WANG

et al.

Biocell, Journal Year: 2022, Volume and Issue: 47(2), P. 351 - 366

Published: Nov. 18, 2022

B and T-lymphocyte attenuator (BTLA) plays an immunosuppressive role by inhibiting T- B-cell functions. BTLA is associated with a variety of diseases, especially cancer immunity. However, the function in various cancers its clinical prognostic value have still not been comprehensively analyzed. This study aimed to identify relationship between from perspectives differences expression, value, immune infiltration, correlation immune-related genes cancers. Data regarding mRNA miRNA lncRNA data patients 33 existing were collected TCGA database. Target that interacts target obtained StarBase Based on bioinformatics analysis methods, types was thoroughly investigated, competing endogenous RNA network BTLA, miRNA, interacting constructed. The Kaplan-Meier (KM) (has-miR-137) completed using KM plotter. expression varied different cancers, statistical significance nine types. plotter analyze overall survival (OS) regression-free prognosis revealed statistically OS 11 out 21 cancers; 8 type also different. Correlation tumor positive gene (CTLA4 PDCD1) expression. Gene Set Enrichment Analysis showed co-expressed mainly act through biological processes pathways, including response regulation, cell surface receptor signaling pathway, antigen binding, receptor-mediated leukocyte migration. has potential as marker for CLL, COAD, NSCLC, OV diagnostic KIRC. close complex occurrence development tumors, immunotherapy worthy further analysis.

Language: Английский

Beyond CTLA-4 and PD-1 Inhibition: Novel Immune Checkpoint Molecules for Melanoma Treatment DOI Open Access
Dimitrios C. Ziogas, Charalampos Theocharopoulos, Panagiotis-Petros Lialios

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(10), P. 2718 - 2718

Published: May 11, 2023

More than ten years after the approval of ipilimumab, immune checkpoint inhibitors (ICIs) against PD-1 and CTLA-4 have been established as most effective treatment for locally advanced or metastatic melanoma, achieving durable responses either monotherapies in combinatorial regimens. However, a considerable proportion patients do not respond experience early relapse, due to multiple parameters that contribute melanoma resistance. The expression other checkpoints beyond molecules remains major mechanism evasion. recent anti-LAG-3 ICI, relatlimab, combination with nivolumab disease, has capitalized on extensive research field highlighted potential further improvement prognosis by synergistically blocking additional targets new ICI-doublets, antibody-drug conjugates, novel modalities. Herein, we provide comprehensive overview presently published molecules, including LAG-3, TIGIT, TIM-3, VISTA, IDO1/IDO2/TDO, CD27/CD70, CD39/73, HVEM/BTLA/CD160 B7-H3. Beginning from their immunomodulatory properties co-inhibitory co-stimulatory receptors, present all therapeutic modalities targeting these tested preclinical clinical settings. Better understanding checkpoint-mediated crosstalk between effector cells is essential generating more strategies augmented response.

Language: Английский

Citations

46
Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy DOI Creative Commons
Christian Sordo‐Bahamonde, Seila Lorenzo‐Herrero, Rocío Granda‐Díaz

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 30, 2023

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, limited overall responses lack reliable predictive biomarkers patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects compelling need unveiling novel targets for that allow expand spectrum ICB-based strategies achieve optimal efficacy benefit patients. This review thoroughly dissects current molecular functional knowledge BTLA/HVEM axis future perspectives become a target immunotherapy. dysregulation is commonly found linked poor prognosis in solid hematological malignancies. Moreover, circulating BTLA been revealed as blood-based biomarker various cancers. On basis, emerges promising prompted rapid development clinical testing anti-BTLA blocking antibody Tifcemalimab/icatolimab first BTLA-targeted therapy ongoing phase I trials with encouraging results preliminary safety profile monotherapy combined other anti-PD-1/PD-L1 therapies. Nevertheless, it anticipated intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved regulation, tumor microenvironment could limit Therefore, in-depth characterization different settings highly recommended adequate design implementation guarantee best outcomes

Language: Английский

Citations

45
The BTLA–HVEM axis restricts CAR T cell efficacy in cancer DOI
Puneeth Guruprasad, Alberto Carturan, Yunlin Zhang

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(6), P. 1020 - 1032

Published: June 1, 2024

Language: Английский

Citations

14
The BTLA-HVEM complex – The future of cancer immunotherapy DOI Creative Commons
Karolina Wojciechowicz, Marta Spodzieja, Anna Wardowska

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116231 - 116231

Published: Feb. 11, 2024

The BTLA-HVEM complex plays a pivotal role in cancer and immunotherapy by regulating immune responses. Dysregulation of BTLA HVEM expression contributes to immunosuppression tumor progression across various types. Targeting the interaction between holds promise for enhancing anti-tumor Disruption this presents valuable avenue advancing strategies. Aberrant adversely affects cell function, particularly T cells, exacerbating evasion mechanisms. Understanding modulating axis represents crucial aspect designing effective immunotherapeutic interventions against cancer. Here, we summarize current knowledge regarding structure function HVEM, along with their each other partners. Moreover, soluble transmembrane forms different types impact on prognosis patients is also discussed. Additionally, inhibitors proteins binding that might be used block are reviewed. All presented data highlight plausible clinical application targeted therapies autoimmune disease management. However, further studies required confirm practical use concept. Despite increasing number reports complex, many aspects its biology still need elucidated. This review can regarded as an encouragement guide follow path research.

Language: Английский

Citations

10
Targeting HVEM-GPT2 axis: a novel approach to T cell activation and metabolic reprogramming in non-small cell lung cancer therapy DOI Creative Commons
Yuanshan Yao, Chunji Chen, Bin Li

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 4, 2025

The modulation of tumor microenvironments through immune checkpoint pathways is pivotal for the development effective cancer immunotherapies. This study aims to explore role HVEM in non-small cell lung (NSCLC) microenvironment. datasets this were directly downloaded from Cancer Genome Atlas (TCGA). Single-cell data sourced Tumor Immune Hub (TISCH). Multiplex immunohistochemistry (mIHC) was used cellular composition and spatial distribution microenvironment KO mice bearing mouse also evaluated. Co-cultured system phenotype assays facilitated examination Jurkat T cells' effect on A549 H1299 cells. Quantitative PCR Western blotting determined gene protein expression, respectively, respiration measured oxygen consumption rate (OCR) assays. Lung cells co-cultured with xenografted into nude evaluate growth metastatic potential. Next, RNA-seq, COIP, Dual-luciferase reporter experiment, CHIP-seq potential underlying mechanism. In our study, we investigated NSCLC its implications immunotherapy. Crucially, HVEM, part necrosis factor receptor superfamily, influences activation, potentially impacting immunotherapeutic outcomes. Using TIDE algorithm, results showcased a link between levels dysfunction patients. Delving deeper microenvironment, found predominantly expressed subpopulations. CD8 + CD4 indicated better prognosis adenocarcinoma tissue microarray using multiplex immunohistochemistry. Activated cells, particularly line, significantly inhibited progression, reducing both proliferation invasion capabilities lines. vivo models reinforced these observations. Manipulating expression revealed essential survival activation. addition, animal experiments importance maintaining activated peripheral immunity inflamed local Furthermore, suggest that metabolic reprogramming, transitioning oxidative phosphorylation aerobic glycolysis. RNA sequencing illuminated relationship GPT2, an enzyme tied amino acid metabolism energetics. Subsequent confirmed HVEM's influence activation mediated regulation GPT2. GATA1 validated regulate Our establishes functionality dynamics, pinpointing HVEM-GPT2 axis as promising target therapy.

Language: Английский

Citations

1
Immune Checkpoint Agonists for Inflammatory Skin Diseases DOI
Matthew D. Vesely,

Paul F. Lizzul,

Paul Klekotka

et al.

Journal of Investigative Dermatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

1
The Role of the CD28 Family Receptors in T-Cell Immunomodulation DOI Open Access
Klaudia Ciesielska-Figlon, Katarzyna A. Lisowska

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1274 - 1274

Published: Jan. 20, 2024

The CD28 family receptors include the CD28, ICOS (inducible co-stimulator), CTLA-4 (cytotoxic T-lymphocyte antigen-4), PD-1 (programmed cell death protein 1), and BTLA (B- attenuator) molecules. They characterize a group of molecules similar to immunoglobulins that control immune response through modulating T-cell activity. Among members, act as enhancers activity, while three others-BTLA, CTLA-4, PD-1-function suppressors. interact with B7 ligands. cooperation between these is essential for controlling course adaptive response, but it also significantly impacts development immune-related diseases. This review introduces reader molecular basis functioning their impact on

Language: Английский

Citations

7
Nature’s Arsenal: Harnessing the Capacity of Phytochemicals to Enhance Immune Checkpoint Inhibitor Therapy of Cancers: An Especial Attention to Brain Malignancies DOI
Amir R. Afshari, Mehdi Sanati,

Seyed Sajad Ahmadi

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216955 - 216955

Published: May 14, 2024

Language: Английский

Citations

5
Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future DOI Creative Commons
Menglu Pan, Huanhuan Zhao,

Ruimin Jin

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 6, 2023

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing mainly involving small blood vessels. It demonstrated that T cells are important in the pathogenesis of AAV, including regulatory (Treg) and helper (Th), especially Th2, Th17, follicular Th (Tfh). In addition, exhaustion predicted favorable prognosis AAV. The immune checkpoints (ICs) consist group co-stimulatory co-inhibitory molecules expressed on surface cells, which maintains balance between activation cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), CD137 common molecules, while programmed cell death 1 (PD-1), cytotoxic lymphocyte-associated molecule 4 (CTLA-4), immunoglobulin (Ig) mucin domain-containing protein 3 (TIM-3), B lymphocyte attenuator (BTLA), V-domain Ig suppressor (VISTA), T‐cell ITIM domain (TIGIT), CD200, gene (LAG-3) belong to molecules. If this was disrupted increased, autoimmune diseases (AIDs) might be induced. Even treatment malignant tumors, by checkpoint inhibitors (ICIs) may result AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting importance ICs AIDs. review, we summarized features AAV immunotherapy using ICIs patients with then reviewed biological characteristics different ICs. Our aim explore potential targets for future

Language: Английский

Citations

11
Causal role of immune cells in IgA nephropathy: a mendelian randomization study DOI Creative Commons

Jinlian Shu,

Yating Ge,

Yonggui Wu

et al.

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: July 22, 2024

Background Previous observational studies have shown that immune cells play an important role in IgA nephropathy. However, the specific causal relationship between two is inconsistent.

Language: Английский

Citations

4