Strong CD8(+) T-cell responses against tumor-associated antigens prolong the recurrence-free interval after tumor treatment in patients with hepatocellular carcinoma.
OBJECTIVE
We investigated whether tumor-specific CD8(+) T-cell responses affect tumor-free survival as well as the relationship between CD8(+) T-cell responses against tumor-associated antigens (TAAs) and the clinical course after tumor treatment in patients with hepatocellular carcinoma (HCC).


METHODS
Twenty patients with HCC that were treated by radiofrequency ablation or trans-catheter chemo-embolization (TACE) and in whom HCC was undetectable by ultrasonography, CT, and/or MRI 1 month after treatment were enrolled in the study. Before and after treatment for HCC, analyses of TAA (glypican-3, NY-ESO-1, and MAGE-1)-specific CD8(+) T-cell responses were evaluated with an interferon-gamma enzyme-linked immunospot (ELISpot) assay using peripheral CD8(+) T-cells, monocytes, and 104 types of 20-mer synthetic peptide overlapping by 10 residues and spanning the entirety of the 3 TAAs.


RESULTS
Sixteen out of 20 patients (80%) showed a positive response (> or = 10 TAA-specific cells/10(5) CD8(+) T-cells) before or after treatment. When we performed univariate analysis of prognostic factors for the tumor-free period in the 20 patients, platelet count, prothrombin time, and the number of TAA-specific CD8(+) T-cells after treatment were significant factors (P = 0.027, 0.030, and 0.004, respectively). In multivariate analysis, the magnitude of the TAA-specific CD8(+) T-cell response (> or = 40 TAA-specific cells/10(5) CD8(+) T-cells) was the only significant prognostic factor for a prolonged tumor-free interval (hazard ratio 0.342, P = 0.022).


CONCLUSIONS
Our results suggest that strong TAA-specific CD8(+) T-cell responses suppress the recurrence of HCC. Immunotherapy to induce TAA-specific cytotoxic T lymphocytes by means such as the use of peptide vaccines should be considered for clinical application in patients with HCC after local therapy.
Hiroishi
Kazumasa
K
Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Eguchi
Junichi
J
Baba
Toshiyuki
T
Shimazaki
Tomoe
T
Ishii
Shigeaki
S
Hiraide
Ayako
A
Sakaki
Masashi
M
Doi
Hiroyoshi
H
Uozumi
Shojiro
S
Omori
Risa
R
Matsumura
Takuya
T
Yanagawa
Tatsuro
T
Ito
Takayoshi
T
Imawari
Michio
M
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D017115:Catheter Ablation / Q000379:methods; D016461:Chemoembolization, Therapeutic / Q000379:methods; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010976:Platelet Count; D011379:Prognosis; D011517:Prothrombin Time
D000951:Antigens, Neoplasm