Drug-induced altered self-presentation increases tumor immunogenicity

Abstract

Anti-human immunodeficiency virus (HIV) drug abacavir (ABC) binds to the specific allele of human leukocyte antigen (HLA-B*57:01) and activates CD8⁺ T cells by presenting altered abnormal peptides. Here, we examined the effect of ABC-induced altered self-presentation by HLA-B*57:01 on immunogenicity of cancer cells and CD8⁺ T-cell-dependent anti-tumor immunity. We established human-mouse chimeric HLA-B*57:01-expressing tumor cell lines (B16F10 and 3LL) and tested the anti-tumor effect of ABC in vivo. ABC treatment inhibited the growth of HLA-B*57:01-expressing tumors by a CD8⁺ T-cell-dependent mechanism. ABC treatment induced CXCR3-dependent infiltration of CD8⁺ T cells into HLA-B*57:01-expressing tumors, and activated those tumor-infiltrating CD8⁺ T cells to proliferate and secrete IFN-γ. The activation of CD8⁺ T cells using drug-induced altered self-presentation may be a new strategy to increase tumor immunogenicity and improve the efficacy of immunotherapy.

Keywords: Abacavir; Altered self-presentation; CD8(+) T cell; Cancer immunotherapy; MHC.