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Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels
Karolinska Inst, Dept Med Huddinge, Ctr Hematol & Regenerat Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, Stockholm, Sweden.;Univ Navarra, Dept Organ & Pharmaceut Chem, Pamplona, Spain..
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2018 (English)In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 8, article id 407Article in journal (Refereed) Published
Abstract [en]

Redox active selenium (Se) compounds at sub toxic doses act as pro-oxidants with cytotoxic effects on tumor cells and are promising future chemotherapeutic agents. However, little is known about how Se compounds affect immune cells in the tumor microenvironment. We demonstrate that the inorganic Se compound selenite and the organic methylseleninic acid (MSA) do not, despite their pro-oxidant function, influence the viability of immune cells, at doses that gives cytotoxic effects in ovarian cancer cell lines. Treatment of the ovarian cancer cell line A2780 with selenite and MSA increases NK cell mediated lysis, and enhances the cytolytic activity of T cells. Increased T cell function was observed after incubation of T cells in preconditioned media from tumor cells treated with MSA, an effect that was coupled to decreased levels of PDL1, HIF-1 alpha, and VEGF. In conclusion, redox active selenium compounds do not kill or inactivate immune cells at doses required for anti-cancer treatment, and we demonstrate that MSA enhances T cell-mediated tumor cell killing via PDL1 and VEGF inhibition.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018. Vol. 8, article id 407
Keywords [en]
selenium, methylseleninic acid, PDL1, VEGF, HIF-1 alpha
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-236007DOI: 10.3389/fonc.2018.00407ISI: 000445882100001OAI: oai:DiVA.org:kth-236007DiVA, id: diva2:1255949
Funder
Swedish Cancer Society, CAN 2016/606Marianne and Marcus Wallenberg FoundationThe Cancer Society in Stockholm
Note

QC 20181015

Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2018-10-15Bibliographically approved

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Uhlin, Michael

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