Open AccessCombination rhIL-15 and Anti-PD-L1 (Avelumab) Enhances HIVGag-Specific CD8 T-Cell Function
Author(s) -
Bruktawit Goshu,
Hui Chen,
Maha Moussa,
Jie Cheng,
Marta Catálfamo
Publication year - 2020
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jiaa269
Subject(s) - cytotoxic t cell , avelumab , cd8 , cxcr3 , immunology , interleukin 15 , biology , interleukin 21 , t cell , immunotherapy , cancer research , immune system , nivolumab , in vitro , chemokine , chemokine receptor , biochemistry
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.