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Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1

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An Erratum to this article was published on 11 October 2014

Abstract

Background

To explore the potential application of placenta-specific PLAC1/Cancer Placenta (CP) 1 antigen for immunotherapy in CRC patients, further identification of the cytotoxic T lymphocyte epitopes from this antigen is necessary.

Methods

We assessed the protein expression of PLAC1/CP1 using a tissue chip and immunochemistry staining in CRC samples. Simultaneously, we predicted four PLAC1/CP1-derived HLA-A*0201-restricted peptides by using reverse immunology methods. Peptide-specific CD8+ T cell responses were assessed by an IFN-γ release ELISPOT assay. Effector CD8+ T cells lyse HLA-A*0201 CRC cell line SW620 was detected in a granzyme-B release ELISPOT cytotoxicity assay.

Results

Our results indicated that PLAC1/CP1 was highly expressed in 56.7 % (55/97) of adenocarcinomas. PLAC1/CP1 protein expression was associated with CRC tumor differentiation, the tumor/node/metastasis stage, and lymph node metastasis. Two of four peptides showed high affinities in an HLA-A2 binding assay. In 66.7 % (6/9) of peripheral blood mononuclear cells of CRC samples with PLAC1/CP1 protein-positive expression, these two peptides, PLAC1/CP1 p41-50 (FMLNNDVCV) and PLAC1/CP1 p69-77 (HAYQFTYRV), were immunogenic in the induction of peptide-specific CD8+ T cell responses as assessed by an IFN-γ release ELISPOT assay. Furthermore, the generated effector CD8+ T cells could specifically lyse the PLAC1/CP1 HLA-A*0201 CRC cell line SW620 in a granzyme-B release ELISPOT cytotoxicity assay.

Conclusions

These results show that the PLAC1/CP1 antigen is a possible prognostic marker of CRC and that PLAC1/CP1 p41-50 and PLAC1/CP1 p69-77 are novel HLA-A*0201-restricted CD8+ T cell epitopes and potential targets for peptide-based immunotherapy in CRC patients.

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Acknowledgments

This article supported by grants from the National Natural Science Fund of China (No. 30801093).

Conflict of interest

All the authors have read and approved the final manuscript. No potential conflicts do exist.

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Authors and Affiliations

  1. Department of Pathology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China

    Fangfang Liu, Danhua Shen & Qiujing Song

  2. Department of Hepatology Institute, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China

    Henghui Zhang & Hongsong Chen

  3. Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China

    Shan Wang & Yingjiang Ye

  4. Department of Immunology, Peking University Health Science Center, Beijing, 100083, People’s Republic of China

    Xuewen Pang

  5. Department of Central Laboratoty, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China

    Peiying He

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  1. Fangfang Liu
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  2. Henghui Zhang
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  3. Danhua Shen
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  4. Shan Wang
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  6. Hongsong Chen
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  7. Xuewen Pang
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  8. Qiujing Song
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  9. Peiying He
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Corresponding author

Correspondence to Fangfang Liu.

Additional information

F. Liu and H. Zhang contributed equally to this paper.

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Liu, F., Zhang, H., Shen, D. et al. Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1. J Gastroenterol 49, 419–426 (2014). https://doi.org/10.1007/s00535-013-0811-4

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  • DOI: https://doi.org/10.1007/s00535-013-0811-4

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