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J Gastroenterol. 2014 Mar;49(3):419-26. doi: 10.1007/s00535-013-0811-4. Epub 2013 Apr 21.

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

Author information

1
Department of Pathology, Peking University People's Hospital, Beijing, 100044, People's Republic of China, liufangfang@pkuph.edu.cn.

Erratum in

  • J Gastroenterol. 2014 Dec;49(12):1589.

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.

PMID:
23604623
DOI:
10.1007/s00535-013-0811-4
[Indexed for MEDLINE]

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