Treating Hepatobiliary Cancer: The Immunologic Approach

Duffy, Austin G.; Greten, Tim F.

doi:10.1159/000456593

Cited by 6 publications

(7 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primary liver cancer is the third leading cause of cancer-related deaths globally, accounting for approximately 782,500 deaths annually. Hepatocellular carcinoma (HCC) is the most predominant type of primary liver cancer, comprising about 90% of cases ( 1 , 2 ). The incidence of HCC is increasing, from 14 million cases worldwide in 2012 to an estimated 22 million cases in 2030 ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Wen

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.

show abstract

Section: Introductionmentioning

confidence: 99%

Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Wen

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Therefore, novel methods of accurately determining individual patient-specific prognosis based on clinical, biological, and genetic factors have been proposed. 1,[7][8][9][10] In turn, these factors may be incorporated into traditional clinical tools for predicting long-term patient outcomes, as well as guide the choice of appropriate treatment strategies. 11,12 The prognostic nutritional index (PNI) is a simple marker of individual nutrition and inflammation levels based on serum albumin concentration and total lymphocyte count, both of which can be easily obtained with routine preoperative blood tests.…”

Section: Discussionmentioning

confidence: 99%

Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection

Akgül

Bagante

Olsen

et al. 2018

Journal of Surgical Oncology

View full text Add to dashboard Cite

BackgroundIntrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long‐term overall survival among patients with ICC who underwent curative‐intent resection.MethodsPatients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi‐institutional database. Clinic‐pathological characteristics and long‐term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses.ResultsAmong 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5‐year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008).ConclusionA low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis.

show abstract

“…The metabolism, phenotype, and function of immune cells are affected by the presence and level of the nutrition molecules in the TME, such as fatty acids and glucose, which is the concept of "immunometabolism." Glucose deficiency and lactic acid abundance in the TME limit the activity of CTLs, and enhancement of fatty acid oxidation (FAO) blocks the cytotoxicity of CTLs in tumors, whereas Treg cells use FAO instead of glycolysis, so these cells survive in glucose-deficient and hypoxic environments and suppress the tumor-killing function of CTLs (1,2,5). Elevated aerobic glycolysis, gluconeogenesis, and b-oxidation of fatty acids, along with reduced TCA cycle activity, are major metabolic alterations in liver cancer.…”

Section: Metabolic Situation In Hcc and The Role Of Tim-3mentioning

confidence: 99%

“…The term "hepatobiliary cancer" refers to primary malignancies in the liver, either hepatocellular carcinoma (HCC) or the intra-and extra-hepatic biliary ductal system, giving rise to biliary tract carcinomas (BTC). HCC is the predominant type of primary liver cancer, which comprises approximately 90% of cases, whereas BTCs are rare tumors (1)(2)(3). Surgery plays a substantial role in the cure in the early stages of the disease and is restricted to a minority of patients with localized diseases; however, most HCC patients are diagnosed at advanced stages when therapeutic options are limited, and apart from locoregional or systemic therapies, recurrence happens in most of them within 5 years.…”

Section: Introductionmentioning

confidence: 99%

“…Understanding the immunometabolic situation of T lymphocytes and other immune cells, along with the metabolic behavior of cancer cells, can help us to design new therapeutic approaches against cancers (3,5). On the other hand, the role of the immune system and immune checkpoint inhibitors in HCC is taken into consideration in recent studies, and they have shown significant progress in the last few years (1,2). Accordingly, one of the main strategies to improve the specific immune response to the tumor is to use monoclonal antibodies to block the immune checkpoint (1,3).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of TIM-3 in Hepatocellular Carcinoma: A Promising Target for Immunotherapy?

et al. 2020

View full text Add to dashboard Cite

One of the most common tumors in the world is hepatocellular carcinoma (HCC), and its mortality rates are still on the rise, so addressing it is considered an important challenge for universal health. Despite the various treatments that have been developed over the past decades, the prognosis for advanced liver cancer is still poor. Recently, tumor immunotherapy has opened new opportunities for suppression of tumor progression, recurrence, and metastasis. Besides this, investigation into this malignancy due to high immune checkpoint expression and the change of immunometabolic programming in immune cells and tumor cells is highly considered. Because anti-cytotoxic T lymphocyte–associated protein (CTLA)-4 antibodies and anti-programmed cell death protein (PD)-1 antibodies have shown therapeutic effects in various cancers, studies have shown that T cell immunoglobulin mucin-3 (TIM-3), a new immune checkpoint molecule, plays an important role in the development of HCC. In this review, we summarize the recent findings on signal transduction events of TIM-3, its role as a checkpoint target for HCC therapy, and the immunometabolic situation in the progression of HCC.

show abstract

Treating Hepatobiliary Cancer: The Immunologic Approach

Cited by 6 publications

References 62 publications

Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection

The Role of TIM-3 in Hepatocellular Carcinoma: A Promising Target for Immunotherapy?

Contact Info

Product

Resources

About