Preferential Recognition of Drug-Induced Altered Self-Presentation on Tumor Cells, but Not Host Cells, by CD8⁺ T Cells for Eliciting Anti-Tumor Immunity

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We previously reported that CD8⁺ T cell activation via drug-induced altered self-presentation increases the tumor immunogenicity and cancer immunotherapy efficacy. Although the anti-human immunodeficiency virus drug abacavir (ABC) increases the tumor immunogenicity and induces CD8⁺ T cell anti-tumor immune responses in mice inoculated with tumor cells ectopically expressing the human leukocyte antigen (HLA)-B*57:01, whether such anti-tumor immunity is also triggered in hosts with high HLA-B*57:01 expression levels remain unclear. To verify this, we investigated the anti-tumor effects of ABC on HLA-B*57:01-expressing tumor and normal host cells using HLA-B*57:01 transgenic (B*57:01-Tg) mice in this study. ABC suppressed the HLA-B*57:01-expressing B16F10 tumor growth and increased the CD8⁺ T cell tumor infiltration in B*57:01-Tg mice. ABC also activated the tumor-infiltrating CD8⁺ T cells to secrete interferon-γ but did not promote their proliferation in the tumors of B*57:01-Tg mice. Moreover, ABC did not increase the effector CD8⁺ T cell proportions in the tumor-draining lymph nodes of B*57:01-Tg mice. Overall, CD8⁺ T cells preferentially recognized the ABC-induced altered self-antigen-presenting HLA-B*57:01-expressing tumor cells, but not host cells, to elicit anti-tumor immunity.