Immunotherapy in hepatocellular carcinoma

SummaryHepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers. The prognosis remains poor —the 5‑year overall-survival (OS) is 12–18%, all stages taken together. Systemic therapy has been limited to the use of tyrosine kinase inhibitors for more than a decade. Now immune therapy has also arrived in the field of systemic HCC treatment. Despite initial enthusiasm, the response rate to single agent immune checkpoint blockade (ICB) in HCC patients is approximately 15–20%. The immune tolerance of the liver and cirrhosis-associated immune dysfunction (CAID) may play a role in the immunological tumor escape phenomenon. The two phase 3 trials of pembrolizumab vs. placebo in seco nd-line treatment (KEYNOTE-240) and nivolumab vs. sorafenib in first-line treatment (CheckMate 459) did not reach their primary endpoint of OS benefit. Pleasant news from IMbrave150 were recently published: the combination therapy of atezolizumab and bevacizumab reached significant benefit in overal l response rate (ORR) and overall survival (OS) compared to current standard of care (SOC) sorafenib in patients advanced HCC in first-line therapy.
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research

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AbstractFunctional rescue of NK-cells in solid tumors represents a central aim for new immunotherapeutic strategies. We have conducted a genomic, phenotypic and functional analysis of circulating NK-cells from patients with HCV-related liver cirrhosis and hepatocellular carcinoma. NK-cells were sorted from patients with HCC or liver cirrhosis and from healthy donors. Comparative mRNA gene expression profiling by whole-human-genome microarrays of sorted NK-cells was followed by phenotypic and functional characterization. To further identify possible mediators of NK-cell dysfunction, an in vitro model using media conditioned...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Mondelli Hepatocellular carcinoma (HCC) still represents a significant complication of chronic liver disease, particularly when cirrhosis ensues. Current treatment options include surgery, loco-regional procedures and chemotherapy, according to specific clinical practice guidelines. Immunotherapy with check-point inhibitors, aimed at rescuing T-cells from exhaustion, has been applied as second-line therapy with limited and variable success. Natural killer (NK) cells are an essential component of innate immunity against cancer and changes in phenotype and function have been described in patients with HCC, who also show...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
      ·Application is being reviewed under FDA ’s Real-Time Oncology Review pilot programmeBasel, 27 January 2020 – Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced the completion of a supplemental Biologics License Application (sBLA) submission to the US Food and Drug Administration (FDA) for Tecentriq® (atezolizumab) in combination with Avastin® (bevacizumab), for the treatment of people with unresectab le hepatocellular carcinoma (HCC) who have not received prior systemic therapy. The FDA is reviewing the application under the Real-Time Oncology Review pilot programme, wh...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
Semin Liver Dis DOI: 10.1055/s-0039-3399534Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20%), with mixed ...
Source: Seminars in Liver Disease - Category: Gastroenterology Authors: Tags: Review Article Source Type: research
In conclusion, PD-1+ TIGIT+ CD8+ T-cell populations are associated with accelerated disease progression and poor outcomes in HBV-HCC, which might not only have important clinical implications for prognosis but also provide a rationale for new targets in immunotherapy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractHepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and syst...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
caens Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults and has one of the highest mortality rates of solid cancers. Ninety percent of HCCs are associated with liver fibrosis or cirrhosis developed from chronic liver injuries. The immune system of the liver contributes to the severity of the necrotic-inflammatory tissue damage, the establishment of fibrosis and cirrhosis, and the disease progression towards HCC. Immunotherapies have emerged as an exciting strategy for HCC treatment, but their effect is limited, and an extensive translation research is urgently needed to enhance anti-tumor...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resect...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Joanna Mikulak1,2, Elena Bruni1,2, Ferdinando Oriolo1,2, Clara Di Vito1 and Domenico Mavilio1,2* 1Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Milan, Italy 2Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy The liver is considered a preferential tissue for NK cells residency. In humans, almost 50% of all intrahepatic lymphocytes are NK cells that are strongly imprinted in a liver-specific manner and show a broad spectrum of cellular heterogeneity. Hepatic NK (he-NK) cells play key roles in tuning liver immune response in b...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion: In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future. Introduction Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related deaths (Jemal et al., 2011). Chronic inflammation, caused by chemical, biological and physical factors, is found to be related to certain human cancers. The effe...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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