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Identification of ribosomal proteins S2 and L10a as tumor antigens recognized by HLA-A26-restricted CTL
1Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan.
Abstract:
Recent identification of cytotoxic T lymphocyte (CTL)-directed peptides binding to the HLA-A2 and -A24 alleles has opened the door to peptide-based cancer immunotherapies. However, subsequent studies have succeeded in identifying no more than a few CTL-directed peptides that bind to alleles other than HLA-A2 and -A24, thus hampering development of immunotherapies directed at other alleles. We have shown in this study that two genes coding for ribosomal proteins (S2 and L10a) encoded tumor antigens recognized by HLA-A26-restricted CTLs. The S2 mRNA was expressed in all of the cancer cells and non-malignant cell lines tested, but was not expressed in normal tissues except for the testis, muscle, and peripheral mononuclear leukocyte cell (PBMC). In contrast, the L10a mRNA was expressed in all of these cancer and non-malignant cell lines, and also normal tissues, although the expression levels in normal tissues were mostly low. One S2-derived peptide and two L10a-derived peptides had the ability to induce HLA-A26-restricted and peptide-specific CTLs reactive to tumor cells in PBMCs of cancer patients, respectively. These ribosomal protein-derived peptides, and particularly the S2-derived peptide, could be suitable for use in peptide-based immunotherapy for HLA-A26+ cancer patients.
Insights
Researchers identified novel tumor antigens from ribosomal proteins S2 and L10a. These peptides can stimulate cytotoxic T lymphocytes (CTLs) for potential HLA-A26 cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Peptide-based cancer immunotherapies are emerging, but limited to specific HLA alleles like HLA-A2 and -A24.
- Development of immunotherapies for other HLA alleles is hindered by a lack of identified target peptides.
Purpose of the Study:
- To identify novel tumor antigens recognized by HLA-A26-restricted cytotoxic T lymphocytes (CTLs).
- To evaluate the potential of these antigens for developing peptide-based cancer immunotherapies targeting HLA-A26+ patients.
Main Methods:
- Analysis of ribosomal protein genes (S2 and L10a) as potential tumor antigen sources.
- Assessment of S2 and L10a mRNA expression in cancer cell lines, non-malignant cell lines, and normal tissues.
- Identification and testing of S2- and L10a-derived peptides for their ability to induce HLA-A26-restricted, tumor-specific CTL responses in cancer patient PBMCs.
Main Results:
- Two ribosomal protein genes, S2 and L10a, were identified as encoding tumor antigens recognized by HLA-A26-restricted CTLs.
- S2 mRNA showed restricted expression in normal tissues (testis, muscle, PBMCs), while L10a mRNA was more broadly expressed but at lower levels in normal tissues.
- One S2-derived peptide and two L10a-derived peptides successfully induced HLA-A26-restricted, peptide-specific CTLs reactive to tumor cells from cancer patient PBMCs.
Conclusions:
- Ribosomal protein-derived peptides, particularly from S2, are promising candidates for peptide-based immunotherapy in HLA-A26+ cancer patients.
- This study expands the repertoire of targetable tumor antigens for cancer immunotherapy beyond HLA-A2 and -A24 alleles.
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