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Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3+ regulatory T cells.

ABSTRACT: Tumor-infiltrating lymphocytes (TILs) represent the host immune response to a tumor. In this study, we investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in liver transplant candidates with hepatocellular carcinoma (HCC) and established an improved prognostic model for predicting clinical outcome. CD3+, CD4+, CD8+, and FoxP3+ TILs were assessed by immunohistochemistry in tumor tissue from 153 patients who had undergone liver transplantation for HCC. Prognostic effects of these TIL subsets and other clinicopathologic factors were evaluated by Kaplan-Meier and Cox regression analysis. The area under the curve (AUC) and net reclassification improvement (NRI) were calculated to determine if the new model improved risk prediction. We found that the prevalence of intra-tumoral FoxP3+ Tregs among CD4+ TILs, but not the density of intra-tumoral FoxP3+ Tregs, was an independent predictor for disease-free (DFS) and overall survival (OS) (P<0.05). A Cox model combining the prevalence of intra-tumoral FoxP3+ Tregs with Hangzhou criteria was highly predictive of tumor recurrence and death. The AUCs of the Cox model for recurrence (0.733; 95% CI, 0.656-0.802) and survival (0.765; 95% CI, 0.690-0.830) were significantly increased when compared with those of Hangzhou criteria (P<0.001). Net reclassification improvement showed that predictability of the Cox models for both recurrence and survival was superior to Hangzhou criteria (P<0.05). Our results collectively showed that the prevalence of intra-tumoral FoxP3+ Tregs is a promising prognostic predictor for HCC patients after OLT. Inclusion of FoxP3+ Tregs into Hangzhou criteria could improveme risk prediction.

SUBMITTER: Chen K

PROVIDER: S-EPMC6958165 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3+ regulatory T cells.

Chen Kangjie K Guo Haijun H Zheng Shusen S

International journal of clinical and experimental pathology 20180301 3

Tumor-infiltrating lymphocytes (TILs) represent the host immune response to a tumor. In this study, we investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in liver transplant candidates with hepatocellular carcinoma (HCC) and established an improved prognostic model for predicting clinical outcome. CD3+, CD4+, CD8+, and FoxP3+ TILs were assessed by immunohistochemistry in tumor tissue from 153 patients who had undergone liver tra ...[more]

PMID: 31938228

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Project description:Introduction: Several attempts have been made to expand the indications of liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria. We aimed to define genomic features that enable the identification of patients with HCC beyond Milan criteria who have acceptable transplant outcomes. Methods: Among 770 consecutive HCC patients transplanted at Mount Sinai Hospital and Mayo Clinic between 1990 and 2013, 132 had tumors exceeding Milan criteria on pathology and were enrolled in the study. Explant tumors were analyzed to assess genomic signatures of poor prognosis and immunohistochemical markers associated with tumor recurrence and overall survival. Results: Most of the patients were males (80%) and HCV positive (71%) with a median age of 56. HCC beyond Milan criteria was defined pre-operative in 67%. On pathology, 44% of the patients satisfied the ‘up-to-7 rule’. At a median follow-up of 88 months, 64 patients had died and 45 recurred; the 5-year overall survival (OS) and recurrence rates were 57% and 35%, respectively. CK19 gene signature was independently associated with recurrence (HR=2.95, p<0.001), along with tumor size >5 cm (HR=3.37, p=0.023) and presence of satellite lesions (HR=2.98, p=0.001). S2 subclass signature, which is known to be associated with progenitor cell markers, was independently associated with poor OS (HR=3.18, p=0.001), along with tumor size >5 cm (HR=5.06, p<0.001) and outside up-to-seven rule (HR=2.50, p=0.002). Using the presence of markers of progenitor cells (either CK19 or S2 subclass signatures) patients may be classified into poor-prognosis (n=58; 5-year recurrence 53%, survival 45%) and good-prognosis subgroups (n=74; 5-year recurrence 19%, survival 67%) (HR=3.16, p<0.001 for recurrence, and HR=1.72, p=0.04 for OS). Conclusion: Gene signatures associated with progenitor cell markers (CK19 and S2 subclass signatures) define outcome of HCC patients beyond Milan criteria after transplantation. Patients without these signatures achieve survival rates similar as those patients within Milan criteria. Once prospectively validated, these markers may provide the rationale for a limited expansion of liver transplantation indications.

Dataset Information

Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3+ regulatory T cells.

Publications

Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3<sup>+</sup> regulatory T cells.

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