Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer DOI Open Access
Lifeng Li, Liping Wang,

Jieyao Li

et al.

Cancer Research, Journal Year: 2018, Volume and Issue: 78(7), P. 1779 - 1791

Published: Jan. 26, 2018

Abstract Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor activity, yet the mechanisms underlying this activity remain unclear. We show here metformin treatment blocks suppressive function of myeloid-derived suppressor cells (MDSC) in patients with ovarian cancer by downregulating expression and ectoenzymatic CD39 CD73 on monocytic polymononuclear MDSC subsets. triggered activation AMP-activated protein kinase α subsequently suppressed hypoxia-inducible factor α, which was critical induction CD39/CD73 MDSC. Furthermore, correlated longer overall survival diabetic cancer, accompanied metformin-induced reduction frequency circulating CD39+CD73+ concomitant increase activities CD8+ T cells. Our results highlight direct effect suggest may yield clinical benefit through improvement T-cell immunity dampening CD39/CD73-dependent immunosuppression patients. Significance: The an antidiabetes attributable to reduced immunosuppressive tumor Cancer Res; 78(7); 1779–91. ©2018 AACR.

Language: Английский

The tumour microenvironment in pancreatic cancer — clinical challenges and opportunities DOI
Won Jin Ho, Elizabeth M. Jaffee, Lei Zheng

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(9), P. 527 - 540

Published: May 12, 2020

Language: Английский

Citations

902
Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System DOI Creative Commons
Thomas S. Postler, Sankar Ghosh

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(1), P. 110 - 130

Published: June 15, 2017

Language: Английский

Citations

729
Targeting immunosuppressive adenosine in cancer DOI

Dipti Vijayan,

Arabella Young, Michele W.L. Teng

et al.

Nature reviews. Cancer, Journal Year: 2017, Volume and Issue: 17(12), P. 709 - 724

Published: Oct. 23, 2017

Language: Английский

Citations

692
Metabolism of immune cells in cancer DOI
Robert D. Leone, Jonathan D. Powell

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(9), P. 516 - 531

Published: July 6, 2020

Language: Английский

Citations

618
Extracellular ATP and P2 purinergic signalling in the tumour microenvironment DOI
Francesco Di Virgilio, Alba Clara Sarti, Simonetta Falzoni

et al.

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(10), P. 601 - 618

Published: July 13, 2018

Language: Английский

Citations

599
Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer DOI Creative Commons
Kai Li,

Houhui Shi,

Benxia Zhang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Oct. 7, 2021

Abstract Myeloid-derived suppressor cells (MDSCs) are a heterogenic population of immature myeloid with immunosuppressive effects, which undergo massive expansion during tumor progression. These not only support immune escape directly but also promote invasion via various non-immunological activities. Besides, this group proved to impair the efficiency current antitumor strategies such as chemotherapy, radiotherapy, and immunotherapy. Therefore, MDSCs considered potential therapeutic targets for cancer therapy. Treatment targeting have shown promising outcomes in both preclinical studies clinical trials when administrated alone, or combination other anticancer therapies. In review, we shed new light on recent advances biological characteristics functions MDSCs. We hope propose an overview MDSCs-targeting therapies so provide ideas treatment.

Language: Английский

Citations

547
Natural killer cells in antitumour adoptive cell immunotherapy DOI Open Access
Tamara Laskowski, Alexander Biederstädt, Katayoun Rezvani

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(10), P. 557 - 575

Published: July 25, 2022

Language: Английский

Citations

497
The hallmarks of successful anticancer immunotherapy DOI Open Access
Lorenzo Galluzzi, Timothy A. Chan, Guido Kroemer

et al.

Science Translational Medicine, Journal Year: 2018, Volume and Issue: 10(459)

Published: Sept. 19, 2018

Various features of the tumor and immune system influence success immunotherapy.

Language: Английский

Citations

495
Targeting adenosine for cancer immunotherapy DOI Creative Commons
Robert D. Leone, Leisha A. Emens

Journal for ImmunoTherapy of Cancer, Journal Year: 2018, Volume and Issue: 6(1)

Published: June 18, 2018

Immune checkpoint antagonists (CTLA-4 and PD-1/PD-L1) CAR T-cell therapies generate unparalleled durable responses in several cancers have firmly established immunotherapy as a new pillar of cancer therapy. To extend the impact to more patients broader range cancers, targeting additional mechanisms tumor immune evasion will be critical. Adenosine signaling has emerged key metabolic pathway that regulates immunity. is an immunosuppressive metabolite produced at high levels within microenvironment. Hypoxia, cell turnover, expression CD39 CD73 are important factors adenosine production. through A2a receptor expressed on cells potently dampens inflamed tissues. In this article, we describe role regulating immunity, highlighting potential therapeutic targets pathway. We also review preclinical data for each target provide update current clinical activity field. Together, suggest rational combination strategies incorporate inhibitors hypoxia-CD39-CD73-A2aR great promise further improving outcomes patients.

Language: Английский

Citations

469
The adenosine pathway in immuno-oncology DOI
Bertrand Allard, David Allard, Laurence Buisseret

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(10), P. 611 - 629

Published: June 8, 2020

Language: Английский

Citations

411