Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression

Samuel T. Haile, Sonia P. Dalal, Virginia Clements, Koji Tamada, Suzanne Ostrand-Rosenberg

Research output: Contribution to journalArticlepeer-review

Abstract

Many tumor cells escape anti-tumor immunity through their expression of programmed death ligand-1 (PDL1 or B7-H1), which interacts with T cell-expressed PD1 and results in T cell apoptosis. We previously reported that transfection of human tumor cells with a membrane-bound form of the human costimulatory molecule CD80 prevented PD1 binding and restored T cell activation. We now report that a membrane-bound form of murine CD80 similarly reduces PDL1-PD1-mediated suppression by mouse tumor cells and that a soluble protein consisting of the extracellular domains of human or mouse CD80 fused to the Fc domain of IgG1 (CD80-Fc) overcomes PDL1-mediated suppression by human and mouse tumor cells, respectively. T cell activation experiments with human and mouse tumor cells indicate that CD80-Fc facilitates T cell activation by binding to PDL1 to inhibit PDL1- PD1 interactions and by costimulating through CD28. CD80-Fc is more effective in preventing PD1-PDL1-mediated suppression and restoring T cell activation compared with treatment with mAb to either PD1 or PDL1. These studies identify CD80-Fc as an alternative and potentially more efficacious therapeutic agent for overcoming PDL1-induced immune suppression and facilitating tumor-specific immunity.

Original languageEnglish (US)
Pages (from-to)2829-2836
Number of pages8
JournalJournal of Immunology
Volume191
Issue number5
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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