Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape DOI Creative Commons
Qinghua Wu, You Li, Eugenie Nepovimová

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 3, 2022

Hypoxia, a common feature of the tumor microenvironment in various types cancers, weakens cytotoxic T cell function and causes recruitment regulatory cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia hypoxia-inducible factors (HIFs) 1 2 alpha (HIF1A HIF2A) are involved immune escape. Under hypoxia, activation HIF1A induces series signaling events, including through programmed death receptor-1/programmed ligand-1. Moreover, triggers shedding complex class I chain-associated molecules nitric oxide impairment to disrupt surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances escape via increased cell-platelet binding. HIF2A upregulates stem factor expression recruit tumor-infiltrating mast cells increase levels cytokines interleukin-10 transforming growth factor-β, resulting an immunosuppressive microenvironment. Additionally, tumor-associated long noncoding RNAs suppresses function, enabling Overall, elucidating underlying mechanisms which HIFs promote evasion will allow for targeting HIF treatment. This review discusses current knowledge how facilitate escape, with evidence date implicating as molecular target such provides further insight into mechanism strategies immunotherapy suggested.

Language: Английский

Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway DOI Open Access
Qian Wu, Jiang Li, Sicheng Li

et al.

Acta Pharmacologica Sinica, Journal Year: 2020, Volume and Issue: 42(1), P. 1 - 9

Published: March 9, 2020

Language: Английский

Citations

302
The role of extracellular vesicles in cancer DOI Creative Commons
Raghu Kalluri, Kathleen M. McAndrews

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1610 - 1626

Published: April 1, 2023

Language: Английский

Citations

298
The role of exosomal PD-L1 in tumor progression and immunotherapy DOI Creative Commons
Feiting Xie,

Mengxue Xu,

Jian Lu

et al.

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Oct. 23, 2019

Abstract Programmed death ligand 1 (PD-L1), a type I transmembrane protein, binds to its receptor PD-1 suppress the activation of T cells, thereby maintaining immunological homeostasis. In contrast, tumor cells highly express PD-L1, which expressed on activated leading immune escape. Anti-PD-1/PD-L1 checkpoint therapy blocks binding PD-1/PD-L1 reinvigorate exhausted inhibiting growth. Exosomes are biologically active lipid-bilayer nanovesicles secreted by various cell types that mediate intercellular signal communication. Numerous studies have shown able promote epithelial-mesenchymal transition, angiogenesis, and escape releasing exosomes. Recent imply tumor-derived exosomes could carry PD-L1 in same membrane topology as surface, resisting therapy. this review, we mainly discuss role regulation progression potential resistance mechanism immunotherapy via exosomal PD-L1. addition, propose may be target overcome anti-PD-1/PD-L1 antibody

Language: Английский

Citations

291
Extracellular vesicles as tools and targets in therapy for diseases DOI Creative Commons

Mudasir A. Kumar,

Sadaf Khursheed Baba,

Hana Q. Sadida

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 5, 2024

Abstract Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers ubiquitously released from cells under normal pathological conditions. Human serum is a rich source of these EVs, though their isolation proteins non-EV lipid particles poses challenges. These transport various cellular components such as proteins, mRNAs, miRNAs, DNA, lipids across distances, influencing numerous physiological events, including those within tumor microenvironment (TME). Their pivotal roles in communication make EVs promising candidates for therapeutic agents, drug delivery systems, disease biomarkers. Especially cancer diagnostics, EV detection can pave way early identification offers potential diagnostic Moreover, subtypes emerging targeted tools, highlighting clinical significance. The need non-invasive biomarkers to monitor biological processes purposes remains unfulfilled. Tapping unique composition could unlock advanced avenues future. In this review, we discuss detail conditions, cancers (encompassing head neck, lung, gastric, breast, hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune renal diseases, emphasizing advancements molecular diagnostics delivery.

Language: Английский

Citations

291
Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape DOI Creative Commons
Qinghua Wu, You Li, Eugenie Nepovimová

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 3, 2022

Hypoxia, a common feature of the tumor microenvironment in various types cancers, weakens cytotoxic T cell function and causes recruitment regulatory cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia hypoxia-inducible factors (HIFs) 1 2 alpha (HIF1A HIF2A) are involved immune escape. Under hypoxia, activation HIF1A induces series signaling events, including through programmed death receptor-1/programmed ligand-1. Moreover, triggers shedding complex class I chain-associated molecules nitric oxide impairment to disrupt surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances escape via increased cell-platelet binding. HIF2A upregulates stem factor expression recruit tumor-infiltrating mast cells increase levels cytokines interleukin-10 transforming growth factor-β, resulting an immunosuppressive microenvironment. Additionally, tumor-associated long noncoding RNAs suppresses function, enabling Overall, elucidating underlying mechanisms which HIFs promote evasion will allow for targeting HIF treatment. This review discusses current knowledge how facilitate escape, with evidence date implicating as molecular target such provides further insight into mechanism strategies immunotherapy suggested.

Language: Английский

Citations

261