scholarly journals Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma

Gut ◽  
2018 ◽  
Vol 68 (2) ◽  
pp. 335-346 ◽  
Author(s):  
Valerie Chew ◽  
Yun Hua Lee ◽  
Lu Pan ◽  
Nurul J M Nasir ◽  
Chun Jye Lim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Prediction Model ◽  
Clinical Response ◽  
Immune Activation ◽  
Locally Advanced ◽  
Advanced Hepatocellular Carcinoma ◽  
Systemic Immune Activation ◽  
Before And After ◽  
Yttrium 90

ObjectivesYttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response.DesignTime-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE.ResultsTILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8+ T cells, CD56+ NK cells and CD8+ CD56+ NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB+CD8+ T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8+ and CD4+ T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1+/Tim-3+CD8+ T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs.ConclusionHigh-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment.

scholarly journals Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hidenari Nagai ◽  
Takanori Mukozu ◽  
Daigo Matsui ◽  
Takenori Kanekawa ◽  
Masahiro Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Liver Cirrhosis ◽  
Antitumor Immunity ◽  
Host Immunity ◽  
Th2 Cells ◽  
Host Immune System ◽  
Advanced Hepatocellular Carcinoma ◽  
Before And After ◽  
Significant Change

Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy.Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood samples were collected before and after treatment.Results. Eleven patients were treated with sorafenib at 200 mg/day (200 group), 27 patients received sorafenib at 400 mg/day (400 group), and 7 patients were given sorafenib at 800 mg/day (800 group). There was no significant change in the percentage of Th1 cells after treatment in any group. However, the percentages of Th2 cells and regulatory T cells were significantly decreased after treatment in the 400 group and 800 group compared with before treatment, although there was no significant change after treatment in the 200 group.Conclusions. These results indicate that treatment with sorafenib might induce Th1 dominance and prevent the escape of tumor cells from the host immune system in LC patients with aHCC.

Yttrium-90 radioembolization vs sorafenib for intermediate-locally advanced hepatocellular carcinoma: a cohort study with propensity score analysis

2014 ◽  
Vol 35 (3) ◽  
pp. 1036-1047 ◽  
Author(s):  
Annagiulia Gramenzi ◽  
Rita Golfieri ◽  
Cristina Mosconi ◽  
Alberta Cappelli ◽  
Alessandro Granito ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cohort Study ◽  
Propensity Score ◽  
Propensity Score Analysis ◽  
Locally Advanced ◽  
Advanced Hepatocellular Carcinoma ◽  
Score Analysis ◽  
Yttrium 90

scholarly journals Integrated immunological analysis of a successful conversion of locally advanced hepatocellular carcinoma to resectability with neoadjuvant therapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000932
Author(s):  
Won Jin Ho ◽  
Gaurav Sharma ◽  
Qingfeng Zhu ◽  
Genevieve Stein-O'Brien ◽  
Jennifer Durham ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Locally Advanced ◽  
Post Treatment ◽  
Alpha Fetoprotein ◽  
Effector Memory ◽  
Functional Markers ◽  
Preoperative Treatment ◽  
Advanced Hepatocellular Carcinoma ◽  
Immunological Analysis

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide with a minority of patients being diagnosed early enough for curative-intent interventions. We report the first use of preoperative cabozantinib plus nivolumab to successfully downstage what presented as unresectable HCC as part of an ongoing phase 1b study. Preoperative treatment with cabozantinib and nivolumab led to >99% reduction in alpha-fetoprotein, −37.3% radiographic reduction by RECIST 1.1 and a near complete pathologic response (80% to 100% necrosis). An integrated immunological analysis was performed on the post-treatment surgical tumor sample and matched pre-treatment and post-treatment peripheral blood samples with high-dimensional imaging and cytometry techniques. Bayesian non-negative matrix factorization (CoGAPS, Coordinated Gene Activity in Pattern Sets) and self-organizing map (FlowSOM) algorithms were used to distinguish changes in functional markers across cellular neighborhoods in the single cell data sets. Brisk immunological infiltration into the tumor microenvironment was observed in non-random, organized cellular neighborhoods. Systemically, combination therapy led to marked promotion of effector cytotoxic T cells and effector memory helper T cells. Natural killer cells also increased with therapy. The patient remains without disease recurrence and with a normal alpha-fetoprotein approximately 2 years from presentation. Our study provides proof-of-concept that borderline resectable or locally advanced HCC warrants consideration of downstaging with effective neoadjuvant systemic therapy for subsequent curative resection.

BCLC subclassification and tumour characteristics to provide prognostication of outcomes in an Asian population of locally advanced hepatocellular carcinoma treated using selective internal radiation therapy with Yttrium-90.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 443-443
Author(s):  
Eshani Nastassia Mathew ◽  
Nivedita Nadkarni ◽  
Su-Pin Choo ◽  
Han Chong Toh ◽  
David Wai-Meng Tai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Locally Advanced ◽  
Survival Outcomes ◽  
Advanced Hepatocellular Carcinoma ◽  
Selective Internal Radiation Therapy ◽  
Portal Vein Invasion ◽  
Internal Radiation ◽  
Tumour Location ◽  
Yttrium 90

443 Background: Selective internal radiation therapy (SIRT) with Yttrium-90 (Y90) is preferentially used in locally advanced hepatocellular carcinoma (HCC) patients in the Barcelona clinic liver cancer (BCLC) B or C cohort. However, the BCLC B cohort has a wide heterogeneity. To address this, Bolondi et al. proposed a BCLC B subclassification system. Additionally, the BCLC C cohort is also diverse in their Child-Pugh (CP) stage and extent of portal vein thrombosis (PVT). The effect of these subclassifications on survival outcomes has not been studied in HCC patients treated using SIRT. Methods: 392 HCC patients treated using SIRT from 1st January 2008 to 17th March 2017 were analyzed. These patients were classified according to the proposed subclassification system for the BCLC B cohort, and CP stage for the BCLC C cohort, and their survival outcomes reviewed. Results: 293 patients met the study’s inclusion criteria. For B1/B2/B3/B4/ C CP-A and C CP-B, the median OS was 48.3/28.7/14.4/13.7/12.8 and 6.6 months respectively. Overall comparison between the subgroups for median OS reached statistical significance (p < 0.001). The Cox proportional-hazards regression analysis found that tumour location defined as unilobar or bilobar disease significantly influenced median OS. In the BCLC C cohort, the extent of portal vein invasion significantly influenced median OS (p < 0.001). For the BCLC C CP-A group, median OS for segmental/sectoral branch invasion, right and/or left portal vein invasion and main portal vein trunk invasion was 24.1, 12.8 and 6.5 months respectively. Conclusions: Bolondi et al.’s subclassification system optimizes prognostic prediction by reducing the clinical heterogeneity in BCLC B HCC patients treated using SIRT. However tumour location, unaccounted for in the proposed subclassification, is also an important prognosticator. For the BCLC C cohort CP stage, extent of PVT, and tumour location were important predictors of treatment outcomes.

scholarly journals En bloc transdiaphragmatic lung resection for locally advanced hepatocellular carcinoma: a case report

2020 ◽  
Vol 2020 (6) ◽  
Author(s):  
Kit-fai Lee ◽  
Randolph H L Wong ◽  
Howard H W Leung ◽  
Eugene Y J Lo ◽  
Charing C N Chong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Locally Advanced ◽  
Left Lung ◽  
Lower Lobe ◽  
Uneventful Recovery ◽  
Advanced Hepatocellular Carcinoma ◽  
Right Hepatectomy ◽  
En Bloc ◽  
Liver Recurrence ◽  
Lung Base

Abstract A 56-year-old man presented with an 11-cm hepatocellular carcinoma (HCC) at segment 7 of liver. To induce left liver hypertrophy, a sequential transarterial chemoembolization (TACE) and portal vein embolization before right hepatectomy were adopted. However, the tumor further increased in size despite TACE and invaded through the diaphragm to the right lung base. Anterior approach right hepatectomy with en bloc wedge resection of the involved right lower lobe of lung by endovascular staplers via transdiaphragmatic approach was performed. The diaphragmatic defect was closed with Goretex mesh. Patient made an uneventful recovery. Pathology confirmed a 12.5 cm poorly differentiated HCC invading through diaphragm to lung. During follow-up, patient developed a 6 cm recurrence at left lung base 17 months after surgery for which he received sorafenib therapy. However, the lung mass further increased in size with new liver recurrence at segment 3 despite treatment. He succumbed 2 years and 3 months after surgery.

FRI-489-Downstaging by 90-yttrium radioembolization of unresectable locally advanced hepatocellular carcinoma: A single center experience

2019 ◽  
Vol 70 (1) ◽  
pp. e614
Author(s):  
Carolina Martelletti ◽  
Margherita Diotallevi ◽  
Amedeo Calvo ◽  
Nadia Russolillo ◽  
Alessandro Ferrero ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Locally Advanced ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Single Center Experience
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