Topoisomerase I inhibitor, irinotecan, depletes regulatory T cells and up-regulates MHC class I and PD-L1 expression, resulting in a supra-additive antitumor effect when combined with anti-PD-L1 antibodies

Oncotarget
Toshiki IwaiKaname Yamamoto

Abstract

Anti-PD-L1 antibodies inhibit interactions between PD-L1 and PD-1 and interactions between PD-L1 and B7-1, thereby reinvigorating anticancer immunity. Although there are numerous ongoing clinical studies evaluating combinations of standard chemotherapies and anti-PD-L1 antibodies, irinotecan has not yet been investigated in this context so there is little information about its compatibility with anti-PD-L1 antibodies. Here we investigated the efficacy of anti-PD-L1 antibody in combination with irinotecan and the role of irinotecan in the tumor-immunity cycle in an FM3A murine tumor model. Despite a transient decrease in lymphocytes in the peripheral blood after irinotecan treatment, the antitumor activity of anti-PD-L1 antibody plus irinotecan was significantly greater than each agent alone. Irinotecan in combination with anti-PD-L1 antibody enhanced proliferation of CD8+ cells in both tumors and lymph nodes, and the number of tumor-infiltrating CD8+ cells was higher than either irinotecan or anti-PD-L1 antibody monotherapy. Irinotecan was found to decrease the number of Tregs in lymph nodes and tumors, and specific depletion of Tregs by anti-folate receptor 4 antibodies was found to enhance the proliferation of CD8+ cells in t...Continue Reading

References

Jan 11, 2002·The New England Journal of Medicine·Kazumasa NodaUNKNOWN Japan Clinical Oncology Group
Mar 27, 2003·Nature Reviews. Immunology·Matthias G von Herrath, Leonard C Harrison
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Edith A PerezShaker R Dakhil
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ramaswamy GovindanUNKNOWN Cancer and Leukemia Group B (CALGB 30101)
Feb 7, 2009·Nature Reviews. Immunology·Dmitry I Gabrilovich, Srinivas Nagaraj
Apr 29, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rikiya NakamuraMasaru Miyazaki
May 26, 2011·Journal of Translational Medicine·Ioannis AlagkiozidisGeorge Coukos
Dec 19, 2015·Cancer Cell·Lorenzo GalluzziGuido Kroemer
Jan 10, 2017·Frontiers in Immunology·Anja DererUdo S Gaipl
Jan 22, 2018·Pharmacology & Therapeutics·Matthen MathewNaiyer A Rizvi

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Citations

Apr 29, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rajen ModyRochelle Bagatell
Oct 12, 2019·F1000Research·Mary-Ann Bjornsti, Scott H Kaufmann
Aug 9, 2020·Cancer Management and Research·Marissa LamEva Segelov
Aug 16, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Christian Bailly
Dec 31, 2020·Cell Reports Medicine·Neda JabbariQiang Tian
Mar 24, 2021·Journal of Clinical Pathology·Kate WilkinsonCheok Soon Lee
Apr 24, 2021·Genes & Development·Domenic PilgerStephen P Jackson
Feb 17, 2020·NAR Cancer·Christian BaillyBruno Quesnel

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Methods Mentioned

BETA
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FlowJo
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