Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer DOI Creative Commons
Qiang Li,

huii Zhang,

Leilei Zhang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 11, 2023

Abstract The use of oncolytic viruses as a gene therapy vector is an area active biomedical research, particularly in the context cancer treatment. However, actual therapeutic success this approach to tumor elimination remains limited. As such, present study was developed with goal simultaneously enhancing antitumor efficacy and local immune response by combining Ad-GD55 adenovirus antibody specific for TIM-3 checkpoint molecule (α-TIM-3). resultant Ad-GD55-α-Tim-3 capable inducing α-TIM-3 expression within hepatoma cells upon infection, exhibited inhibitory superior that when used treat these together induction enhanced intracellular immunity. In vivo experiments revealed Ad-GD55-α-TIM-3 administration sufficient inhibit growth engage more robust simulated microenvironment. may represent viable treatment hepatocellular carcinoma.

Language: Английский

Cancer cell-intrinsic PD-1: Its role in malignant progression and immunotherapy DOI Open Access
Muhua Chen,

Lei Bie,

Ying Jieer

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 167, P. 115514 - 115514

Published: Sept. 15, 2023

Programmed cell death protein-1 (PD-1), also called CD279, is coded by the PDCD1 gene and constitutively expressed on surface of immune cells. As a receptor checkpoint, PD-1 can bind to programmed ligand-1/programmed ligand-2 (PD-L1/PD-L2) in tumor cells, leading evasion. Anti-PD-1 anti-PD-L1 are important components therapy. as an intrinsic variant (iPD-1) cancer cells where it plays roles malignant progression proposed recent studies. However, iPD-1 has received much less attention compared although there unmet medical need for fully elucidating mechanisms actions achieve best response immunotherapy. suppresses tumorigenesis non-small lung (NSCLC) colon cancer, whereas promotes melanoma, hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), thyroid (TC), glioblastoma (GBM), triple-negative breast (TNBC). In this review, we focus role development its molecular mechanisms. We deeply discuss nivolumab-based combined therapy common may explain different therapeutic effects anti-PD-1 treatment provide critical information use anti-tumor approaches.

Language: Английский

Citations

24
Soluble Immune Checkpoint Protein and Lipid Network Associations with All-Cause Mortality Risk: Trans-Omics for Precision Medicine (TOPMed) Program DOI
Annabelle Rodríguez, Chaojie Yang, Weiniu Gan

et al.

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

Published: Jan. 9, 2025

Adverse cardiovascular events are emerging with the use of immune checkpoint therapies in oncology. Using datasets Trans-Omics for Precision Medicine program (Multi-Ethnic Study Atherosclerosis, Jackson Heart [JHS], and Framingham Study), we examined association plasma proteins each other, their associated protein network high-density lipoprotein cholesterol (HDL-C) low-density (LDL-C), HDL-C- LDL-C-associated networks all-cause mortality risk. Plasma levels LAG3 HAVCR2 showed statistically significant associations Colocalization analysis using genome wide-association studies HDL-C or LDL-C quantitative trait loci from JHS Atherosclerosis Risk Communities identified TFF3 rs60467699 CD36 rs3211938 variants as significantly colocalized HDL-C; contrast, none LDL-C. The measurement LAG3, HAVCR2, plus targeted genotyping may identify patients at increased

Language: Английский

Citations

0
RECQL4 affects MHC class II‐mediated signalling and favours an immune‐evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma DOI Creative Commons
Sara Egea‐Rodriguez, Renáta Váraljai, Thierry M. Nordmann

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 1, 2025

Language: Английский

Citations

0
Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond DOI
Durre Aden, Samreen Zaheer, Niti Sureka

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155864 - 155864

Published: March 1, 2025

Language: Английский

Citations

0
Characterization of alternative sPD-1 isoforms reveals that ECD sPD-1 signature predicts an efficient antitumor response DOI Creative Commons
Ping Hou, Li Hu, Junrong Zhang

et al.

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 11, 2025

Language: Английский

Citations

0
Interaction of the Immune System TIM‐3 Protein with a Model Cellular Membrane Containing Phosphatidyl‐Serine Lipids DOI Creative Commons

Anastasiia Delova,

Andréea Pasc, Antonio Monari

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(22)

Published: Feb. 12, 2024

Abstract T cell transmembrane, Immunoglobulin, and Mucin (TIM) are important immune system proteins which especially present in T‐cells regulated the by sensing engulfment apoptotic processes. Their role is exerted capacity to detect presence of phosphatidyl–serine lipid polar head outer leaflet cellular membranes (correlated with apoptosis). In this contribution using equilibrium enhanced sampling molecular dynamics simulation we unravel bases thermodynamics TIM, particular TIM‐3, interaction phosphatidyl serine a bilayer. Since TIM‐3 deregulation an factor pro‐oncogenic tumor micro‐environment understanding its functioning at level may pave way development original immunotherapeutic approaches.

Language: Английский

Citations

3
Soluble immune checkpoint molecules: mechanism of formation, function, role in malignant neoplasms DOI Creative Commons
Glazanova Tv, Irina Pavlovа, E. V. Kuzmich

et al.

Medical Immunology (Russia), Journal Year: 2025, Volume and Issue: 27(1), P. 21 - 34

Published: Jan. 8, 2025

Immune checkpoints (ICs) represent a broad set of stimulatory and inhibitory signaling pathways playing an important role in regulation immune responses. Initially, ICs have been considered solely as cell membrane-bound receptor ligand systems, triggering or blocking function. Over the past decade they proven to exist soluble forms (sICs). sICs are biologically active regulators involved paracrine systemic modulation responses, similar cytokines. Normally, exert both effects on system, their balance may be disturbed many malignant neoplasms, COVID-19, HIV infection. There is lot data connection between various diseases, but number key aspects biology not fully clarified. The most widely studied PD-1 (programmed death receptor-1) its ligands PD-L1 PD-L2, CTLA-4 (cytotoxic T lymphocyte antigen-4), TIM-3 (T immunoglobulin mucin-domain containing-3), VISTA (V-domain Ig-containing suppressor activation). mechanisms form formation complex diverse include alternative splicing, cleavage membrane ectodomains, proteolytic cleavage. molecular underlying synthesis release sPD-1 sPD-L1 splicing mRNA translation isoforms lacking transmembrane domains, while sTIM-3 occurs by cleaving extracellular regions proteins protease ADAM10. review article provides main sICs, including sPD-1, sPD-L1, exosomal sCTLA-4, several others. formation, biological functions maintaining homeostasis, prognostic significance changes content described patients with solid tumors (nonsmall lung cancer, hepatocellular breast kidney skin gastric etc.), well for hematologic malignancies (lymphoma, chronic lymphocytic leukemia, acute myeloblastic multiple myeloma).

Language: Английский

Citations

0
Post-transplant Inflammatory Bowel Disease Associated with Donor-Derived TIM-3 Deficiency DOI Creative Commons

Adrian Baldrich,

Dominic Althaus,

Thomas Menter

et al.

Journal of Clinical Immunology, Journal Year: 2024, Volume and Issue: 44(3)

Published: Feb. 16, 2024

Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There currently no systematic effort exclude loss- or gain-of-function mutations in immune-related genes donors. This despite the fact that more than 100 inborn errors of immunity may cause contribute IBD. We have molecularly characterized patient who developed fulminant inflammatory aSCT with stable 100% donor-derived hematopoiesis. A pathogenic c.A291G; p.I97M HAVCR2 mutation encoding immune checkpoint protein TIM-3 was identified patient's blood-derived DNA, while being absent DNA derived from skin. expression much decreased serum, and vitro-activated patient-derived T cells expressed reduced levels. In contrast, cell-intrinsic CD25 production cytokines were preserved. barely detectable intestinal mucosa, detected unambiguously inflamed non-inflamed colon unrelated individuals. conclusion, we report first case acquired, "transplanted" insufficiency regulatory linked post-aSCT

Language: Английский

Citations

2
N-glycosylation reinforces interaction of immune checkpoint TIM-3 with a small molecule ligand DOI Creative Commons
Gérard Vergoten, Christian Bailly

Computational Biology and Chemistry, Journal Year: 2023, Volume and Issue: 104, P. 107852 - 107852

Published: March 22, 2023

Language: Английский

Citations

4
Soluble form of immune checkpoints in autoimmune diseases DOI
利正 浅原, Yuxia Wang,

Xuxia Shen

et al.

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 147, P. 103278 - 103278

Published: June 28, 2024

Language: Английский

Citations

1