Tumor-infiltrating Lymphocytes and Prognosis of Hepatocellular Carcinoma

1992 ◽  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

Association of the ratio of CD8+ and CD163+ lymphocytes with clinical outcome in hepatocellular carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15613-e15613
Author(s):  
Huan Chen ◽  
Haibei Xin ◽  
Lihong Wu ◽  
Yanhui Chen ◽  
Hongli Luo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcome ◽  
Cancer Progression ◽  
Immune Cell ◽  
Association Studies ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Disease Recurrence ◽  
Macrophage Density ◽  
Infiltrating Lymphocytes

e15613 Background: Within the tumor microenvironment (TME), infiltrating lymphocytes and myeloid cells including tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) are key players involved in liver cancer progression. The purpose of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+, CD163+ and CD66B+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well paratumor stroma area, were analyzed by multiple immunohistochemistry. Results: Hierarchical clustering analysis of immune cell densities revealed that all HCC samples can be classified into three distinct groups. The three immune oncology types (IO-types) were characterized by a strong CD8 T cell density in CA and SA region (IO-1), an intermediate state of CD8 and CD163+ (IO-2), and a strong CD163+ macrophage density in IO-3. Remarkably increasing risks of mortality and recurrence, as well as elevated AST, ALP, GGT and AFP levels, were identified in IO-3 group, when compared with IO-1 group. We then identified that percentages of CA-CD8+ TILs in the tumor sample and SA-CD163+ macrophages in the para-tumor region showed opposite distribution pattern among the three IO types, suggesting a predictive role for CD8/TAM ratio in HCC cohort. Therefore, we next classified all HCC samples into two subgroups, according to the levels of tumor-CA-CD8/paratumor-SA-CD163 ratio. Expectedly, higher rate of CD8/CD163 represented significantly improved overall survival (OS) and progression free survival (PFS), verses lower rate of CD8/CD163. Further association studies suggested that the two subgroups correlated with HBV DNA, tumor size, and microvascular invasion (MVI). Of note, a prognostic signature combining portal vein tumor thrombus (PVTT) and CD8/CD163 ratio discriminated HCC patients into four subtypes with increasing risk of mortality and recurrence. Conclusions: The current results indicated that the CD8/CD163 is a novel, independent prognostic factor for a lower rate of disease recurrence and favorable OS in patients with resectable HCC.

scholarly journals Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Dan Wang ◽  
Linlin Huang ◽  
Xiaojing Zhang ◽  
Pingping Sun ◽  
Yapeng Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Chronic Hepatitis ◽  
Mrna Expression ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Regression Analysis ◽  
Nuclear Respiratory Factor ◽  
Immune Infiltration ◽  
Nuclear Respiratory Factor 1 ◽  
Infiltrating Lymphocytes

Abstract Background: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its prognostic value and tumor-infiltrating lymphocytes association. Here, we evaluated the association among expression of NRF1, clinicopathological characteristics, survival and immune infiltration in hepatocellular carcinoma (HCC).Methods: We used the Tumor Immune Estimation Resource (TIMER) to analyze the difference of NRF1 mRNA expression in human cancers. Clinical-pathological information and follow-up data were collected from HCC (n = 171) and chronic hepatitis (n = 113) patients. NRF1 expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slides. Correlations between clinical features and the expression of NRF1 were evaluated by Chi-square test, Kaplan-Meier curves, logrank tests and multivariate Cox regression analysis. The correlations between NRF1 expression and gene marker sets of tumor infiltrating lymphocytes (TILs) were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Results: NRF1 mRNA expression was significantly higher in HCC than in normal tissue. Compared with chronic hepatitis, more frequency of NRF1 high expression are found in HCC (31.58 % vs 13.27 %, P < 0.001, P < 0.001). In addition, the NRF1 expression was significantly associated with hepatic cirrhosis (P = 0.021) and vascular invasion (P = 0.025). NRF1 expression was also a significant independent predictor of survival in HCC (P = 0.003; HRadj = 0.20; 95% CI = 0.09 – 0.44). NRF1 showed positively correlated with TILs, including B cell (r = 0.384, P = 1.68e-13), CD8+ T cells (r = 0.246, P = 3.99e-06), CD4+ T cells (r = 0.535, P = 6.90e-27), macrophage (r = 0.506, P = 1.52e-23), neutrophils (r = 0.465, P = 6.08e-20) and dendritic cell (r = 0.404, P = 8.61e-15). The marker genes of TILs correlated significantly with NRF1 expression.Conclusions: NRF1 expression was a useful independent prognostic factor and correlated with tumor immune infiltration in HCC.

Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor-infiltrating lymphocytes

2006 ◽  
Vol 0 (0) ◽  
pp. 060726060227001-??? ◽  
Author(s):  
Seitaro Hirano ◽  
Yukio Iwashita ◽  
Atsushi Sasaki ◽  
Seiichiro Kai ◽  
Masayuki Ohta ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals BTBD10 is a Prognostic Biomarker Correlated With Immune Infiltration in Hepatocellular Carcinoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Jianhui Li ◽  
Xiaojuan Tian ◽  
Ye Nie ◽  
Ying He ◽  
Wenlong Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Tumor Infiltrating Lymphocytes ◽  
Normal Liver ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Phosphatase 2A ◽  
Cancer Genome Atlas ◽  
Infiltrating Lymphocytes ◽  
The Impact

Background: BTBD10 serves as an activator of Akt family members through decreasing the protein phosphatase 2A-mediated dephosphorylation. The present study attempted to investigate the prognostic value of BTBD10 in hepatocellular carcinoma (HCC), specially, its relationship with tumor-infiltrating lymphocytes (TILs).Methods: BTBD10 expression was evaluated in HCC using The Cancer Genome Atlas (TCGA) and Xijing Hospital database, and verified in HCC cell lines. Cox analyses were performed to analyze independent prognostic risk factors for HCC. The optimal cut-off value of BTBD10 was calculated, by which all patients were divided into two groups to compare the overall survival (OS). The signaling pathways were predicted, by which BTBD10 may affect the progression of HCC. To investigate the impact of BTBD10 on HCC immunotherapy, correlations between BTBD10 and TILs, immune checkpoints, m6A methylation-related genes and ferroptosis-related genes were assessed. The distribution of half-maximal inhibitory concentration (IC50) of diverse targeted drugs was observed based on the differential expression of BTBD10.Results: BTBD10 expression was higher in HCC tissues and cell lines than that of normal liver tissues and cells. The patients with high expression of BTBD10 showed a worse OS, as compared to that of BTBD10 low-expressing group. Cox analyses indicated that BTBD10 was an independent prognostic risk factor for HCC. Several molecular pathways of immune responses were activated in HCC patients with high-expressing of BTBD10. Furthermore, BTBD10 expression was demonstrated to be positively correlated with tumor-infiltrating B cells, T cells, macrophages, neutrophils and dendritic cells. Meanwhile, the expression of BTBD10 was synchronized with that of several m6A methylation-related genes, ferroptosis-related genes and immune checkpoints. The IC50 scores of Sorafenib, Navitoclax, Veliparib, Luminespib, and Imatinib were found to be lower in BTBD10 high-expressing HCC group.Conclusion: BTBD10 negatively regulates tumor immunity in HCC and exhibits adverse effect on the prognosis of HCC, which could be a potential target for immunotherapy.

scholarly journals Progression on the Roles and Mechanisms of Tumor-Infiltrating T Lymphocytes in Patients With Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoqin Zheng ◽  
Wenjie Jin ◽  
Shanshan Wang ◽  
Huiguo Ding
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Primary Liver Cancer ◽  
Tumor Resection ◽  
Tumor Infiltrating Lymphocytes ◽  
High Recurrence Rate ◽  
Targeted Agents ◽  
Poor Survival ◽  
Infiltrating Lymphocytes

Primary liver cancer (PLC) is one of the most common malignancies in China, where it ranks second in mortality and fifth in morbidity. Currently, liver transplantation, hepatic tumor resection, radiofrequency ablation, and molecular-targeted agents are the major treatments for hepatocellular carcinoma (HCC). Overall, HCC has a poor survival rate and a high recurrence rate. Tumor-infiltrating lymphocytes (TILs) have been discovered to play essential roles in the development, prognosis, and immunotherapy treatment of HCC. As the major component cells of TILs, T cells are also proved to show antitumor and protumor effects in HCC. Foxp3+, CD8+, CD3+, and CD4+ T lymphocytes are the broadly studied subgroups of TILs. This article reviews the roles and mechanisms of different tumor-infiltrating T lymphocyte subtypes in HCC.

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