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

The biology , function , and biomedical applications of exosomes DOI Open Access
Raghu Kalluri, Valerie S. LeBleu

Science, Journal Year: 2020, Volume and Issue: 367(6478)

Published: Feb. 7, 2020

Clinical uses of cellular communication Exosomes are a type extracellular vesicle that contain constituents (protein, DNA, and RNA) the cells secrete them. They taken up by distant cells, where they can affect cell function behavior. Intercellular through exosomes seems to be involved in pathogenesis various disorders, including cancer, neurodegeneration, inflammatory diseases. In Review, Kalluri LeBleu discuss biogenesis disease, highlighting areas more research is needed. also potential clinical applications exosome profiling for diagnostics exosome-mediated delivery therapeutics target disease cells. Science , this issue p. eaau6977

Language: Английский

Citations

7241
The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth DOI Creative Commons
Karin E. de Visser, Johanna A. Joyce

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

Citations

1539
Hallmarks of response, resistance, and toxicity to immune checkpoint blockade DOI Creative Commons
Golnaz Morad, Beth A. Helmink, Padmanee Sharma

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5309 - 5337

Published: Oct. 1, 2021

Language: Английский

Citations

1070
Immune checkpoint signaling and cancer immunotherapy DOI Creative Commons
Xing He, Chenqi Xu

Cell Research, Journal Year: 2020, Volume and Issue: 30(8), P. 660 - 669

Published: May 28, 2020

Abstract Immune checkpoint blockade therapy has become a major weapon in fighting cancer. Antibody drugs, such as anti-PD-1 and anti-PD-L1, demonstrate obvious advantages broad applicability across cancer types durable clinical response when treatment is effective. However, the overall rates are still unsatisfying, especially for cancers with low mutational burden. Moreover, adverse effects, autoimmune symptoms tumor hyperprogression, present significant downside some applications. These challenges reflect urgent need to fully understand basic biology of immune checkpoints. In this review, we discuss regulation signaling at multiple levels provide an overview our current understanding biology. Topics include surface expression known proteins via delivery, internalization, recycling, degradation. Upon reaching surface, checkpoints engage both conventional trans also cis interactions ligands induce regulate responses. Novel therapeutic strategies targeting these pathways addition classical have recently emerged been tested preclinical models, providing new avenues developing next-generation immunotherapies.

Language: Английский

Citations

977
<p>Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications</p> DOI Creative Commons
Yi Zhang,

Jia-Yao Bi,

Jiayi Huang

et al.

International Journal of Nanomedicine, Journal Year: 2020, Volume and Issue: Volume 15, P. 6917 - 6934

Published: Sept. 1, 2020

Exosomes are nano-sized small extracellular vesicles secreted by cells, carrying nucleic acids, proteins, lipids and other bioactive substances to play a role in the body's physiological pathological processes. Compared synthetic carriers such as liposomes nanoparticles, endogeneity heterogeneity of exosomes give them extensive unique advantages field disease diagnosis treatment. However, storage stability, low yield, purity, weak targeting limit its clinical application. For this reason, further exploration is needed optimize above problems facilitate future functional studies exosomes. In paper, origin, classification, preparation characterization, stability applications exosome delivery system summarized discussed searching large number literatures.

Language: Английский

Citations

919
Mechanisms Controlling PD-L1 Expression in Cancer DOI Creative Commons
Jong‐Ho Cha, Li-Chuan Chan, Chia‐Wei Li

et al.

Molecular Cell, Journal Year: 2019, Volume and Issue: 76(3), P. 359 - 370

Published: Oct. 24, 2019

Language: Английский

Citations

748
The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses DOI Creative Commons
Alireza Labani‐Motlagh,

Mehrnoush Ashja-Mahdavi,

Angelica Loskog

et al.

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: May 15, 2020

The success of cancer immunotherapy relies on the knowledge tumor microenvironment and immune evasion mechanisms in which tumor, stroma infiltrating cells function a complex network. potential barriers that profoundly challenge overall clinical outcome promising therapies need to be fully identified counteracted. Although has increasingly been applied, we are far from understanding how utilize different strategies best way combine therapeutic options optimize benefit. This review intends give contemporary detailed overview roles cells, exosomes molecules acting they relate activation escape. Further, current novel immunotherapeutic will discussed.

Language: Английский

Citations

603
The importance of exosomal PDL1 in tumour immune evasion DOI
Dhouha Daassi, Kathleen M. Mahoney, Gordon J. Freeman

et al.

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(4), P. 209 - 215

Published: Jan. 21, 2020

Language: Английский

Citations

486
Challenges and advances in clinical applications of mesenchymal stromal cells DOI Creative Commons
Tian Zhou, Zenan Yuan, Jianyu Weng

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: Feb. 12, 2021

Mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, majority of registered trials applying MSC therapy diverse human diseases fallen short expectations, despite encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria MSCs identity across studies and their inherited heterogeneity. Nowadays, with emergence advanced biological techniques substantial improvements bio-engineered materials, strategies developed overcome challenges application. Here this review, we will discuss major therapies application, factors impacting diversity MSCs, potential approaches that modify products highest therapeutic potential, finally usage COVID-19 pandemic disease.

Language: Английский

Citations

463
Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source DOI Creative Commons

Wanrong Meng,

Chuanshi He,

Yaying Hao

et al.

Drug Delivery, Journal Year: 2020, Volume and Issue: 27(1), P. 585 - 598

Published: Jan. 1, 2020

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nanosized membrane derived from most cell types. Carrying diverse biomolecules their parent cells, EVs important mediators of intercellular communication thus play significant roles in physiological pathological processes. Owing to natural biogenesis process, generated with high biocompatibility, enhanced stability, limited immunogenicity, which provide multiple advantages as drug delivery systems (DDSs) over traditional synthetic vehicles. have been reported be used for the siRNAs, miRNAs, protein, small molecule drugs, nanoparticles, CRISPR/Cas9 treatment various diseases. As a vectors, can penetrate into tissues bioengineered enhance targetability. Although EVs' characteristics make them ideal delivery, EV-based remains challenging, due lack standardized isolation purification methods, loading efficiency, insufficient clinical grade production. In this review, we summarized current knowledge on application DDS perspective different origin weighted bottlenecks DDS.

Language: Английский

Citations

439