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The predictive value of centre tumour CD8? T cells in patients with hepatocellular carcinoma: comparison with Immunoscore.

ABSTRACT: The increasing evidences suggest that Immunoscore(IS), a combinatorial density analysis of CD8+ and CD3+ cells in the centre and invasive margin of tumour (CT and IM), has an advantage over the currently used tumour staging methods in a variety of tumours; however, IS in hepatocellular carcinoma remains unreported. In this study, IS was performed on serial sections from two HCC cohorts (total 449) and compared with current tumour staging systems. Kaplan-Meier curves illustrate a positive association between a higher IS (IS?2) and longer survival of HCC patients. Although the IS was highly related to the outcome of patients, however, IS seems not to be the optimal prognostic factor when compared with the CD8CT. As noted, among CD8CT, CD8IM, CD3CT, CD3IM and IS, CD8CT, as an independent indicator, demonstrated the highest prognostic impact on both DFS and OS in our Cox multivariate regression analysis (P< 0.0001). In our study, the minimum cut-off value was 93 CD8CT cells per mm2, to be used to divide the patients into CD8CTHi group and CD8CTLo group in clinical settings. Our results suggest that CD8CT densities analysis notably improved the accuracy of survival prediction with convenience of clinical manipulation in HCC.

SUBMITTER: Sun C

PROVIDER: S-EPMC4742128 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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The predictive value of centre tumour CD8⁺ T cells in patients with hepatocellular carcinoma: comparison with Immunoscore.

Sun Cheng C Xu Jing J Song Jiaxi J Liu ChaoQun C Wang Jinyu J Weng Chenchun C Sun Haoyu H Wei Haiming H Xiao Weihua W Sun Rui R Tian Zhigang Z

Oncotarget 20151101 34

The increasing evidences suggest that Immunoscore(IS), a combinatorial density analysis of CD8+ and CD3+ cells in the centre and invasive margin of tumour (CT and IM), has an advantage over the currently used tumour staging methods in a variety of tumours; however, IS in hepatocellular carcinoma remains unreported. In this study, IS was performed on serial sections from two HCC cohorts (total 449) and compared with current tumour staging systems. Kaplan-Meier curves illustrate a positive associa ...[more]

PMID: 26415232

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Project description:In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence-free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including ?-fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C-indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram-predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.

Project description:BackgroundThis study aimed to evaluate the expression status and prognostic role of various immunoregulatory cells and test in triple-negative breast cancer (TNBC).MethodsThe expression of five markers (CD3/CD4/CD8/CD19/CD163) of tumor immune cells was evaluated retrospectively in tumor sections from 68 consecutive cases of TNBC by immunohistochemistry. Computational image analysis was used to quantify the density and distribution of each immune marker within the tumor region, tumor invasive margin, and expression hotspots. Immunoscores were calculated using an automated approach. Other clinical characteristics were also analyzed.ResultsFor all patients, Kaplan-Meier survival analysis showed that high CD3+ signals in the tumor region (disease-free survival (DFS), P=0.0014; overall survival (OS), P=0.0031) and total region (DFS, P=0.0014; OS, P=0.0031) were significantly associated with better survival. High CD4+ levels in the tumor region and total regions were significantly associated with better survival (P<0.05). For Hotspot analysis, CD3+ was associated with significantly better survival for all Top1, Top2, and Top3 densities (DFS and OS, P<0.05). High CD4+ levels were significantly associated with better prognosis for Top1 and Top3 densities (DFS and OS, P<0.05). For stage IIB and IIIC patients, CD3+ in the tumor region and all Top hotspots was found to be significantly correlated with survival (DFS and OS, P<0.05). CD4+ cells were significantly associated with survival in the tumor region, total region, and Top3 density (DFS, P=0.0213; OS, P=0.0728). CD8+ cells were significantly associated with survival in the invasive margin, Top2 density, and Top3 density. Spatial parameter analysis showed that high colocalization of tumor cells and immune cells (CD3+, CD4+, or CD8+) was significantly associated with patient survival.ConclusionComputational image analysis is a reliable tool for evaluating the density and distribution of immune regulatory cells and for calculating the Immunoscore in TNBC. The Immunoscore retains its prognostic significance in TNBC later than IIB stage breast cancer. Future studies are required to confirm its potential to predict tumor responses to chemotherapy and immune therapy.

Dataset Information

The predictive value of centre tumour CD8? T cells in patients with hepatocellular carcinoma: comparison with Immunoscore.

Publications

The predictive value of centre tumour CD8⁺ T cells in patients with hepatocellular carcinoma: comparison with Immunoscore.

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