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
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  • Published online on: Saturday, December 1, 2007
  • Pages: 1463-1468
  • DOI: 10.3892/or.18.6.1463

Abstract

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.
Journal Cover

December 2007
Volume 18 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

2013 Impact Factor: 2.191
Ranked #33/202 Oncology
(total number of cites)

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APA
Komohara, Y., Harada, M., Ishihara, Y., Suekane, S., Noguchi, M., Yamada, A., Matsuoka, K., & Itoh, K. (2007). HLA-G as a target molecule in specific immunotherapy against renal cell carcinoma. Oncology Reports, 18(6), 1463-1468.
MLA
Komohara, Harada, Ishihara, Suekane, Noguchi, Yamada, Matsuoka, and Kyogo Itoh. "HLA-G as a target molecule in specific immunotherapy against renal cell carcinoma." Oncology Reports Oncology Reports 18.6 (2007): 1463-1468.
Chicago
Komohara, Harada, Ishihara, Suekane, Noguchi, Yamada, Matsuoka, and Kyogo Itoh. "HLA-G as a target molecule in specific immunotherapy against renal cell carcinoma." Oncology Reports Oncology Reports 18 no. 6 (2007): 1463-1468.