Regulatory T cells are associated with post-cryoablation prognosis in patients with hepatitis B virus-related hepatocellular carcinoma.
BACKGROUND
We carried out this study to evaluate the association between regulatory T cells (Treg) and prognosis and progression after cryoablation in patients with hepatitis-B virus-related hepatocellular carcinoma.


METHODS
Peripheral Treg frequency in 111 patients with hepatocellular carcinoma (HCC) was detected by flow cytometry. Treg frequency and function were re-examined during patient follow up. A possible association between Treg and α-fetoprotein (AFP) was also analyzed, and the distribution of resident CD4(+) and CD8(+) T cells and FoxP3(+) T cells in the liver tissue of patients with HCC was examined by immunohistochemistry.


RESULTS
Treg frequency significantly increased with disease progression. Our longitudinal study showed that Treg frequency had significantly decreased in 17 patients with HCC regression following cryoablation, but the frequency had dramatically increased in 14 patients with HCC recurrence or progression. Furthermore, AFP levels varied in a way comparable with Treg frequency in patients with elevated AFP recorded before therapy. Significantly increased suppressive effects of Treg on proliferation and cytokine secretion of CD8(+) and CD4(+) T cells were observed during follow up in patients with tumor progression, but not in patients with tumor response. Moreover, the numbers of CD8(+), CD4(+), and FoxP3(+) cells infiltrating the tumors around the cryotherapeutic zones were significantly decreased after argon-helium cryoablation, and this was associated with a reduction in the FoxP3/CD8 ratio. Importantly,increased quantities of circulating CD4(+)CD25(+)FoxP3(+) Treg and tumor infiltrating FoxP3(+) cells before cryoablation were associated with high recurrence or risk of progression in HCC patients after cryoablation.


CONCLUSIONS
Treg variation is associated with tumor regression or progression in HCC following cryoablation and may be used as a marker to estimate HCC progression.
Zhou
Lin
L
Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing 302 Hospital, Beijing 100039, China.
Fu
Jun-Liang
JL
Lu
Yin-Ying
YY
Fu
Bao-Yun
BY
Wang
Chun-Ping
CP
An
Lin-Jing
LJ
Wang
Xin-Zhen
XZ
Zeng
Zhen
Z
Zhou
Chun-Bao
CB
Yang
Yong-Ping
YP
Wang
Fu-Sheng
FS
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000601:surgery* / Q000821:virology; D003452:Cryosurgery / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000601:surgery* / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
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