Dataset Information

Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

ABSTRACT:

Background & aims

Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).

Methods

The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-?) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays using peripheral blood mononuclear cells (PBMCs) in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677).

Results

The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-?-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.

Conclusions

SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.

Trial registration

UMIN000005677.

SUBMITTER: Kaji K

PROVIDER: S-EPMC5256867 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

Kaji Kiichiro K Mizukoshi Eishiro E Yamashita Tatsuya T Arai Kuniaki K Sunagozaka Hajime H Fushimi Kazumi K Nakagawa Hidetoshi H Yamada Kazutoshi K Terashima Takeshi T Kitahara Masaaki M Kaneko Shuichi S

PloS one 20170123 1

<h4>Background & aims</h4>Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).<h4>Methods</h4>The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were u ...[more]

PMID: 28114424

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Project description:The spleen is an important site for extramedullary hematopoiesis and tumor immunotolerance. Spleen weight varies with tumor progression and may be a predictor of tumor recurrence. However, to the best of our knowledge, the association between spleen weight and tumor progression remains unclear. The present study revealed a novel role for the spleen in predicting the cellular immune response in tumor-bearing mice. A murine H22 subcutaneous hepatoma model was established. The spleen weight and tumor weight were measured. The proportion of immune cells in peripheral blood and spleen were detected by flow cytometry. The results demonstrated that the spleen weight of tumor-bearing mice at day 21 was higher than that of the controls. In addition, spleen weight was identified to be positively correlated with tumor weight. The percentages of CD4+ and CD8+ T lymphocytes in the spleen were decreased at day 21 after tumor cell inoculation, while those of monocytic-like myeloid-derived suppressor cells (M-MDSCs) and CD11b+F4/80+ macrophages were increased at day 21 after tumor cell inoculation. Similarly, the percentage of polymorphonuclear-like MDSCs (PMN-MDSCs) in the spleen of tumor-bearing mice was increased at days 7, 14 and 21 after tumor cell inoculation. Notably, spleen weight was negatively correlated with the percentages of CD4+ and CD8+ T lymphocytes in the spleen, although spleen and tumor weight were positively correlated with the percentages of M-MDSCs and PMN-MDSCs in the spleen. Similarly, the percentages of CD8+ T lymphocytes in the peripheral blood were decreased, and programmed cell death protein 1 expression on CD8+ T lymphocytes was increased at day 21 after tumor cell inoculation. Furthermore, the percentages of M-MDSCs were increased at day 21 and PMN-MDSCs in the peripheral blood were increased at days 7, 14 and 21 after tumor cell inoculation. Additionally, spleen and tumor weight were also positively correlated with the percentages of M-MDSC and PMN-MDSCs in the peripheral blood of tumor-bearing mice. Collectively, the findings of the present study suggested that spleen weight may be a predictor of tumor prognosis, since it was directly correlated with tumor weight and the percentages of M-MDSC and PMN-MDSCs in tumor-bearing mice.

Dataset Information

Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

Background & aims

Methods

Results

Conclusions

Trial registration

Publications

Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

Similar Datasets

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