Valproic acid attenuates CCR2-dependent tumor infiltration of monocytic myeloid-derived suppressor cells, limiting tumor progression.

Oncoimmunology
Zhiqi XieMasashi Tachibana

Abstract

Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells that promote tumor progression by inhibiting anti-tumor immunity and may be the cause of patient resistance to immune checkpoint inhibitors (ICIs). Therefore, MDSCs are a promising target for cancer immunotherapy, especially in combination with ICIs. Previous studies have shown that the anticonvulsant drug valproic acid (VPA) has additional anti-cancer and immunoregulatory activities due to its inhibition of histone deacetylases. We have previously shown that VPA can attenuate the immunosuppressive function of differentiated MDSCs in vitro. In the present study, we utilized anti-PD-1-sensitive EL4 and anti-PD-1-resistant B16-F10 tumor-bearing mouse models and investigated the effects of VPA on MDSCs with the aim of enhancing the anti-cancer activity of an anti-PD-1 antibody. We showed that VPA could inhibit EL4 and B16-F10 tumor progression, which was dependent on the immune system. We further demonstrated that VPA down-regulated the expression of CCR2 on monocytic (M)-MDSCs, leading to the reduced infiltration of M-MDSCs into tumors. Importantly, we demonstrated that VPA could relieve the immunosuppressive action of MDSCs on CD8+ T-cell and NK cell proliferat...Continue Reading

References

Nov 14, 1997·The Journal of Biological Chemistry·C Wu
Sep 30, 2010·The Journal of Experimental Medicine·Cesar A CorzoDmitry I Gabrilovich
Feb 15, 2011·International Immunopharmacology·James FinkePeter Cohen
Dec 24, 2011·Nature·Ira MellmanGlenn Dranoff
Mar 6, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Indu R RamachandranYulia Nefedova
Apr 30, 2014·The Journal of Experimental Medicine·Muhammad Zaeem NomanSalem Chouaib
Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·KiBem KimShibin Zhou
Apr 4, 2015·Science·Padmanee Sharma, James P Allison
Aug 21, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christoffer GebhardtViktor Umansky
Sep 2, 2015·The Journal of Clinical Investigation·Stefano UgelVincenzo Bronte
Sep 12, 2015·Cell·Sonja KleffelTobias Schatton
Feb 10, 2016·Trends in Immunology·Vinit KumarDmitry I Gabrilovich
Jul 7, 2016·Nature Communications·Vincenzo BronteDmitry I Gabrilovich
Jul 13, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ashley OrillionRoberto Pili
Sep 8, 2017·Journal of Human Genetics·Miao-Miao ZhuZan-Ling Zhang
Jan 20, 2018·Nature Immunology·Filippo VegliaDmitry Gabrilovich
Jun 27, 2018·Frontiers in Immunology·Rebekka WeberViktor Umansky
Sep 5, 2018·Journal of Pharmacological Sciences·Zhiqi XieMasashi Tachibana
Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Rashmi R Shah
Apr 20, 2019·Journal of Immunology Research·Rodolfo Soria-CastroAlma D Chávez-Blanco
Dec 28, 2019·Proceedings of the National Academy of Sciences of the United States of America·Joseph A Flores-ToroJeffrey K Harrison

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Methods Mentioned

BETA
flow cytometry
FACS
acetylation
histone acetylation

Software Mentioned

GraphPad Prism
FlowJo

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