PMID- 17982631 OWN - NLM STAT- MEDLINE DCOM- 20080123 LR - 20201226 IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 18 IP - 6 DP - 2007 Dec TI - HLA-G as a target molecule in specific immunotherapy against renal cell carcinoma. PG - 1463-8 AB - 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-G(146-154) peptide was found to effectively induce peptide-specific CTLs, and HLA-G(146-154) 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. FAU - Komohara, Yoshihiro AU - Komohara Y AD - Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan. ycomo@kumamoto-u.ac.jp FAU - Harada, Mamoru AU - Harada M FAU - Ishihara, Yuki AU - Ishihara Y FAU - Suekane, Shigetaka AU - Suekane S FAU - Noguchi, Masanori AU - Noguchi M FAU - Yamada, Akira AU - Yamada A FAU - Matsuoka, Kei AU - Matsuoka K FAU - Itoh, Kyogo AU - Itoh K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (HLA Antigens) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A24 Antigen) RN - 0 (HLA-G Antigens) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptide Fragments) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Amino Acid Sequence MH - Carcinoma, Renal Cell/genetics/*immunology/pathology MH - Cell Line, Tumor MH - Flow Cytometry MH - HLA Antigens/*immunology MH - HLA-A Antigens/genetics MH - HLA-A24 Antigen MH - HLA-G Antigens MH - Histocompatibility Antigens Class I/*immunology MH - Humans MH - Immunotherapy/*methods MH - Interferon-gamma/pharmacology MH - Kidney Neoplasms/genetics/*immunology/pathology MH - Peptide Fragments MH - T-Lymphocytes, Cytotoxic/drug effects/immunology EDAT- 2007/11/06 09:00 MHDA- 2008/01/24 09:00 CRDT- 2007/11/06 09:00 PHST- 2007/11/06 09:00 [pubmed] PHST- 2008/01/24 09:00 [medline] PHST- 2007/11/06 09:00 [entrez] PST - ppublish SO - Oncol Rep. 2007 Dec;18(6):1463-8.