An imbalance between stellate cells and γδT cells contributes to hepatocellular carcinoma aggressiveness and recurrence.
PURPOSE
The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC.


METHODS
The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells.


RESULTS
Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells.


CONCLUSIONS
The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.
['Zhou|Bao-Yong|BY|', 'Gong|Jun-Hua|JH|', 'Cai|Xiao-Yan|XY|', 'Wang|Jia-Xing|JX|', 'Luo|Fang|F|', 'Jiang|Ning|N|', 'Gong|Jian-Ping|JP|', 'Du|Cheng-You|CY|', 'Liao|Rui|R|http://orcid.org/0000-0002-0057-2792']
D006528:Carcinoma, Hepatocellular D002452:Cell Count D018572:Disease-Free Survival D005260:Female D055166:Hepatic Stellate Cells D006801:Humans D000075942:Intraepithelial Lymphocytes D008099:Liver D008113:Liver Neoplasms D008297:Male D008875:Middle Aged D009361:Neoplasm Invasiveness D009364:Neoplasm Recurrence, Local D011379:Prognosis D016019:Survival Analysis
γδT cell Hepatocellular carcinoma Hepatic stellate cell Prognosis Circulating tumor cell