Combination rhIL-15 and Anti-PD-L1 (Avelumab) Enhances HIVGag-Specific CD8 T-Cell Function. (20th May 2020)

• Record Type: Journal Article
• Authors: Goshu, Bruktawit A; Chen, Hui; Moussa, Maha; Cheng, Jie; Catalfamo, Marta
• Is Part Of: Journal of infectious diseases. Volume 222:Number 9(2020)
• Page Start: 1540
• Page End: 1549
• Publication Date: 2020-05-20
• Subjects: HIV-specific CD8 T cells -- rhIL-15 -- PD-L1 blockade; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiaa269
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: In chronic HIV infection, virus-specific cytotoxic CD8 T cells showed expression of checkpoint receptors and impaired function. Therefore, restoration of CD8 T-cell function is critical in cure strategies. Here, we show that in vitro blockade of programmed cell death ligand 1 (PD-L1) by an anti-PD-L1 antibody (avelumab) in combination with recombinant human interleukin-15 (rhIL-15) synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells. In addition, these CD8 T cells have a CXCR3 + PD1 −/low phenotype, suggesting a potential to traffic into peripheral tissues. In vitro, proliferating CD8 T cells express PD-L1 suggesting that anti-PD-L1 treatment also targets virus-specific CD8 T cells. Together, these data indicate that rhIL-15/avelumab combination therapy could be a useful strategy to enhance CD8 T-cell function in cure strategies. Abstract : In vitro PD-L1 (avelumab) in combination with rhIL-15 synergistically enhanced cytokine secretion by proliferating HIVGag-specific CD8 T cells with a CXCR3 + PD1 −/low phenotype. In addition, avelumab targeted PD-L1 + proliferating HIVGag-specific CD8 T cells.