The specific immune response to tumor antigen CP1 and its correlation with improved survival in colon cancer patients.
OBJECTIVE
The present study was undertaken to determine the expression of a newly identified tumor antigen cancer-placenta 1 (CP1) in colorectal carcinoma (CRC) and explore the CP1-specific immune response in CRC patients and its correlation with patient survival.


METHODS
CP1 expression was determined by reverse-transcription polymerase chain reaction, immunohistochemistry, and Western blot analysis. Serum antibodies against CP1 were detected by enzyme-linked immunosorbent assay, and T-cell response was measured by interferon-gamma/granzyme-B release enzyme-linked immunospot assays. The HLA-A2-restricted epitopes in CP1 were predicted by bioinformatics and then experimentally validated by enzyme-linked immunospot assay.


RESULTS
CP1 expression was detected in a significant number of CRC tissues, reaching 47.6% at the messenger RNA (mRNA) level and 28.6% at the protein level. Of patients with CP1 mRNA(+) tumors, more than 50% had CP1-responsive CD4(+) and CD8(+) T cells and 30% spontaneous-occurring antibodies against CP1. Further studies revealed 2 dominant HLA-A2-restricted epitopes in the CP1 antigen: p31-39 and p58-66. In a follow-up study up to 33 months after surgery, 9 of the 10 patients with CP1-specific CD8 T-cell response survived, whereas 6 of the 8 nonresponders died. Kaplan-Meier analysis indicated a significant correlation between T-cell response and patient survival.


CONCLUSIONS
CP1 represents a new class of tumor-specific shared antigen. Its high expression in CRC tissues, prevalence of CP1-specific immune responses in CP1 mRNA(+) CRC patients, and positive correlation with survival suggest that the antigen may be a useful target for cancer immunotherapy.
Liu
Fang-Fang
FF
Department of Gastroenterological Surgery, Surgical Oncology Laboratory, Peking University People's Hospital, Beijing, China.
Dong
Xue-Yuan
XY
Pang
Xue-Wen
XW
Xing
Qiao
Q
Wang
Hong-Cheng
HC
Zhang
Hua-Gang
HG
Li
Yan
Y
Yin
Yan-Hui
YH
Fant
Michael
M
Ye
Ying-Jiang
YJ
Shen
Dan-Hua
DH
Zhang
Yu
Y
Wang
Shan
S
Chen
Wei-Feng
WF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D015153:Blotting, Western; D016516:CD4-CD8 Ratio; D002681:China / Q000453:epidemiology; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D016335:Zinc Fingers
D000951:Antigens, Neoplasm; D012334:RNA, Neoplasm