Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients

Chew, Valerie; Tow, Charlene; Teo, Marissa; Wong, Hai Ming; Chan, J K; Gehring, Adam J.; Loh, Marie; Bolze, Alexandre; Quek, Richard; Lee, Victor K.M.; Lee, Kang Hoe; Abastado, Jean-Pierre; Toh, Han Chong; Nardin, Alessandra

doi:10.1016/j.jhep.2009.07.013

Cited by 233 publications

(219 citation statements)

References 33 publications

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“…However, the exact association between a high NLR and poor prognosis has not been fully elucidated. One possible explanation is that patients with an elevated NLR have relative lymphocytopenia, leading to a weaker lymphocyte-mediated immune response to the tumor due to a decreasing T4/T8 ratio (33). As a result, these patients may experience a more rapid tumor progression and, therefore, have a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognostic factors for advanced hepatocellular carcinoma with extrahepatic metastasis

Aino

Sumie

Nishizaki

et al. 2014

Molecular and Clinical Oncology

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Abstract. Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The aim of this study was to evaluate whether there are differences in the clinical characteristics and survival between patients with advanced HCC with extrahepatic metastasis who received and those who did not receive previous treatment. Between April, 1998 and April, 2012, a total of 419 HCC patients with extrahepatic metastasis (81 previously untreated and 338 previously treated) were enrolled in this study. The differences in the clinical characteristics, including metastatic sites, were compared between the two groups. In addition, the prognostic predictors among all the patients and among the 81 previously untreated patients were analyzed. The distribution of the major metastatic sites was similar in the two groups; the most frequent site of extrahepatic metastasis was the lungs, followed by the bones, lymph nodes and adrenal glands. The median survival time (MST) among the 419 patients was 6.8 months. The 1-, 2-, 3-and 5-year survival rates were 31.6, 15.3, 9.5 and 2.3%, respectively. No significant differences in survival were observed between patients who received and those who did not receive previous treatment. The multivariate analysis revealed that the Child-Pugh classification, white blood cell count, neutrophil-lymphocyte ratio (NLR) and primary tumor stage were independent predictors of survival for all the patients and for the 81 previously untreated patients. Differences in the clinical characteristics of patients with advanced HCC with extrahepatic metastasis were identified between patients who received and those who did not receive previous treatment. Furthermore, intrahepatic tumor status, Child-Pugh classification, white blood cell count and NLR were demonstrated to be independent predictors of survival in HCC patients with extrahepatic metastasis. IntroductionHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent advances in imaging technology and implementation of surveillance programs for high-risk patients have led to increased detection of early-stage HCC, making curative therapies possible in some patients (1,2). However, the long-term survival of HCC patients remains unsatisfactory, due to the high frequency of intra-and extrahepatic recurrence (3,4). In particular, the development of advanced HCC with extrahepatic metastasis hinders the use of curative therapies, such as surgical resection or radiofrequency ablation, therefore contributing to poor survival. Prior to the approval of sorafenib, several systemic chemotherapeutic regimens had been evaluated for patients with advanced HCC, although no effective therapeutic protocols were identified (5,6). Two randomized placebo-controlled trials demonstrated a survival benefit associated with sorafenib for patients with advanced HCC, including those with extrahepatic metastasis (7,8). As a result, sorafenib is currently considered to be the standard treatment for advanced HCC in the United States, Europe, Japan ...

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and prognostic factors for advanced hepatocellular carcinoma with extrahepatic metastasis

Aino

Sumie

Nishizaki

et al. 2014

Molecular and Clinical Oncology

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“…TNF was determined to be an independent predictor of survival in a multivariate analysis. 106 The pro-inflammatory cytokines IL-1, IFN-c and TNF were downregulated in livers with metastatic HCC, while the anti-inflammatory cytokines IL-4, IL-5, IL-8 and IL-10 were upregulated. 107 …”

Section: Nkr Expression By Activating Cytokinesmentioning

confidence: 94%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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“…The review of the literature reveals attentiveness to the investigation of TILs in hepatic parenchyma, in primary tumor context -namely hepatocellular carcinoma (HCC) [3,[21][22][23][24][25][26][27][28][29][30][31][32] or in liver metastases (LM) [33][34][35]. Nevertheless, we have to highlight the fact that none of the published studies presented comparative data of CD4+ and CD8+ T lymphocytes in primary versus secondary liver tumors.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of CD4 and CD8 lymphocytes — evidences for different distribution in primary and secondary liver tumors

Giuşcă

Wierzbicki

Amălinei

et al. 2015

Folia Histochem Cytobiol.

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Introduction. The impact of tumor cells on tumor-infiltrating lymphocytes (TILs) in cancer developmentis not yet clarified. Our study analyzed the distribution and prognostic value of CD4+ and CD8+ T lymphocytes in hepatocellular carcinoma (HCC) and liver metastases (LM). Material and methods. Archival tissue specimens of 35 HCC and 39 LM patients were immunohistochemically processed. The number of intratumoral (IT) and peritumoral (PT) CD4+ and CD8+ T cells was quantitatively analyzed. Results.We noted large variances of T lymphocyte subpopulations. Similar number of CD4+ and CD8+ lymphocytes was present in HCC, whereas in LM the number of CD8+ cells was approximately two times higher than CD4+ lymphocytes. A significant prevalence of T cells in PT over IT areas was observed. The prognostic value was demonstrated only for PT CD8+ lymphocytes in LM, their reduced number being associated with shorter survival. Conclusions. The differences between proportions of T lymphocytes within tumor and its environment might be explained by proapoptotic effect of cancer cells on TILs.

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Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients

Cited by 233 publications

References 33 publications

Clinical characteristics and prognostic factors for advanced hepatocellular carcinoma with extrahepatic metastasis

Clinical characteristics and prognostic factors for advanced hepatocellular carcinoma with extrahepatic metastasis

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

Comparative analysis of CD4 and CD8 lymphocytes — evidences for different distribution in primary and secondary liver tumors

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