Abstract 5309: Programmed Death Ligand-1 expression on the cell surface is regulated by Costimulatory Molecule CD80 expressed by cancer vaccines

Abstract

Abstract With the lack of effective treatments for metastatic cancers, the employment of immunotherapies, cell-based vaccines particularly, to activate a patient's own immune system is a promising approach for the treatment of disseminated metastatic cancer. Many tumor cells constitutively express or are induced by Interferonγ (IFNγ) to express the inhibitory molecule Programmed Death Ligand 1 (PDL1). Since many cell-based vaccines are derived from tumor cells, the expression of PDL1 could reduce the therapeutic efficacy of the vaccines. PDL1 binds to its receptor Programmed Death 1 (PD1) on T cells and can signal for either apoptosis of T cells or can prevent their activation. As determined by flow cytometry using three anti-PDL1 monoclonal antibodies (mAb) that detect distinct PDL1 epitopes, and human lung, uveal melanoma, cutaneous melanoma, and breast cancer cells, the over-expression of CD80 blocks constitutive and IFNγ-induced cell surface expression of PDL1. Quantitative analysis of CD80 and PDL1 expression indicates an inverse relationship between PDL1 and CD80. CD80+ tumor cells contain intracellular PDL1, as assessed by flow cytometry, suggesting that CD80 regulates PDL1 at the protein level. Tumor cells transfected with CD80 constructs lacking a cytoplasmic domain or with an irrelevant non-signaling cytoplasmic domain, retain the ability to block PDL1 expression at the cell surface indicating that CD80 does not modulate PDL1 transcription via intracellular signaling. These results suggest that in addition to serving as a costimulatory molecule, CD80 facilitates T cell activation by blocking coinhibitory signals and preventing T cell apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5309.