|HLA-G as a target molecule in specific immunotherapy against renal cell carcinoma|
Authors: Yoshihiro Komohara, Mamoru Harada, Yuki Ishihara, Shigetaka Suekane, Masanori Noguchi, Akira Yamada, Kei Matsuoka, Kyogo Itoh
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. email@example.com
The human leukocyte antigen (HLA)-G molecule can exert immunoregulatory functions. However, its limited tissue distribution and preferential expression in a variety of malignancies suggest the possibility that it could be a target in anti-cancer immunotherapy. In the present study, we tested this possibility by focusing on renal cell carcinoma (RCC) patients, especially those with HLA-A24 alleles. Four HLA-G-derived peptides were prepared based on the binding motif to the HLA-A24 alleles. After a stabilization assay confirmed the binding of these peptides to HLA-A24 molecules, they were screened for the capacity to induce peptide-specific cytotoxic T lymphocytes (CTLs) from peripheral blood mononuclear cells (PBMCs) of HLA-A24+ RCC cancer patients. As a result, the HLA-G146-154 peptide was found to effectively induce peptide-specific CTLs, and HLA-G146-154 peptide-stimulated PBMCs exhibited cytotoxic activity against HLA-G-expressing HLA-A24+ RCC cells. Antibody blocking and cold inhibition experiments confirmed that the cytotoxicity was partially ascribed to peptide-specific and HLA class I-restricted CD8+ T cells. These results indicate that HLA-G-associated immunoregulation can be overcome and that HLA-G peptide-based anti-cancer immunotherapy is feasible.