LAUSR

&NA; Hypoxic tumor microenvironment makes cancer cells to be therapy‐resistant and hypoxia‐inducing factors (HIFs) play a central role in hypoxic adaptation. Especially, renal cell carcinoma (RCC) is often associated with von Hippel‐Lindau (VHL) gene mutations, leading to up‐regulation of HIFs. However, from a different point of view, this suggests the possibility that HIFs could be promising targets in anti‐cancer therapy. In this study, we searched for HIF‐1&agr;‐derived peptides that are able to induce RCC‐reactive cytotoxic T lymphocytes (CTLs) from HLA‐A24+ RCC patients. Among five peptides derived from HIF‐1&agr;, which were prepared based on the binding motif to the HLA‐A24 allele, a HIF‐1&agr;278–287 peptide induced peptide‐specific CTLs from peripheral blood mononuclear cells of HLA‐A24+ RCC patients most effectively. In immunoblot assays, the expression of HIF‐1&agr; was lowly detected in whole and nuclear lysates of RCC cell lines even under normoxia (20% O2), and their expression in whole lysates was increased under hypoxia (1% O2). Additionally, HIF‐1&agr;278–287 peptide‐stimulated T cells showed a higher cytotoxicity against HLA‐A24+ HIF‐1&agr;‐expressing RCC cells than against HLA‐A24− HIF‐1&agr;‐expressing RCC cells. The cytotoxicity was inhibited by the addition of HIF‐1&agr;278–287 peptide‐pulsed cold target cells. Altogether, these results indicate that the HIF‐1&agr;278–287 peptide could be a candidate for peptide‐based anti‐cancer vaccines for HLA‐A24+ RCC patients. HighlightsRenal cell carcinoma (RCC) is often associated with von Hippel‐Lindau (VHL) gene mutations, leading to up‐regulation of HIFs.From a different point of view, this suggests the possibility that HIFs could be promising targets in anti‐cancer therapy.We identified a HIF‐1&agr; 278‐287 peptide as a candidate of anti‐cancer vaccine for HLA‐A24+ RCC patients.