Soluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytes

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dc.contributor.authorHorn, Lucas A.
dc.contributor.authorLong, Tiha M.
dc.contributor.authorAtkinson, Ryan
dc.contributor.authorClements, Virginia
dc.contributor.authorOstrand-Rosenberg, Suzanne
dc.date.accessioned2018-04-17T13:09:51Z
dc.date.available2018-04-17T13:09:51Z
dc.date.issued2018-01
dc.description.abstractTumor cells use various immune-suppressive strategies to overcome antitumor immunity. One such method is tumor expression of programmed death ligand-1 (PD-L1), which triggers apoptotic death or anergy upon binding programmed death-1 (PD-1) on T cells. Our previous in vitro cellular studies with human and mouse PD-L1⁺ tumor cells demonstrated that a soluble form of the costimulatory molecule CD80 prevented PD-L1–mediated immune suppression and restored T-cell activation by binding PD-L1 and blocking interaction with PD-1. We now report that in vivo treatment of established syngeneic PD-L1⁺ CT26 colon carcinoma and B16F10 melanoma tumors with CD80-Fc delays tumor growth and promotes tumor-infiltrating T cells. Studies with PD-1−/− and CD28−/− mice demonstrate that soluble CD80 acts in vivo by simultaneously neutralizing PD-1 suppression and activating through CD28. We also report that soluble CD80 mediates its effects by activating transcription factors EGR1-4, NF-κB, and MAPK, downstream signaling components of the CD28 and T-cell receptor pathways. Soluble CD80 binds to CTLA-4 on activated human peripheral blood mononuclear cells. However, increasing quantities of CTLA-4 antagonist antibodies do not increase T-cell activation. These results indicate that soluble CD80 does not suppress T-cell function through CTLA-4 and suggest that CTLA-4 acts as a decoy receptor for CD80, rather than functioning as a suppressive signaling receptor. Collectively, these studies demonstrate that soluble CD80 has therapeutic efficacy in vivo in mouse tumor systems and that its effects are due to its ability to inhibit PD-1–mediated suppression while concurrently activating T cells through CD28. Cancer Immunol Res; 6(1); 59–68.en_US
dc.description.urihttp://cancerimmunolres.aacrjournals.org/content/6/1/59.longen_US
dc.format.extent37 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/M2RF5KH9Z
dc.identifier.citationHorn, L.A., T. M. Long, R. Atkinson, V. Clements, and S. Ostrand-Rosenberg, 2018. Soluble CD80 protein delays tumor growth and promotes tumor infiltrating lymphocytes. Cancer Immunol. Res. 6:59-68.en_US
dc.identifier.uri10.1158/2326-6066.CIR-17-0026
dc.identifier.urihttp://hdl.handle.net/11603/8767
dc.language.isoen_USen_US
dc.publisherAmerican Association of Cancer Researchen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item may be protected under Title 17 of the U.S. Copyright Law. It is made available by UMBC for non-commercial research and education. For permission to publish or reproduce, please contact the author.
dc.subjecttumor cellsen_US
dc.subjectimmune suppressionen_US
dc.subjectprogrammed death ligand (PD-L1)en_US
dc.subjectCD80en_US
dc.subjectcancer immunotherapy
dc.subjecttumor-induced immune suppression
dc.subjectT cell activation,
dc.titleSoluble CD80 Protein Delays Tumor Growth and Promotes Tumor-Infiltrating Lymphocytesen_US
dc.typeTexten_US

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