Tumor‑infiltrating CD8⁺ T cells as a biomarker for chemotherapy efficacy in unresectable hepatocellular carcinoma

Oncology Letters, Journal Year: 2023, Volume and Issue: 25(6)

Published: April 28, 2023

Atezolizumab plus bevacizumab and lenvatinib are approved frontline therapies for advanced hepatocellular carcinoma (HCC). Patients with HCC continue to have a poor prognosis despite these therapeutic choices. Previous studies reported CD8+ tumor-infiltrating lymphocytes (TILs) as biomarker predict responsiveness systemic chemotherapy. The present study investigated whether evaluating TILs by immunohistochemistry staining of liver tumor biopsy tissues could help the response patients atezolizumab lenvatinib. In total, 39 who underwent were classified into high low groups then divided therapy type. clinical responses treatment in both evaluated each therapy. There 12 high-level low-level among those received bevacizumab. An improved rate was observed group compared group. had significantly longer median progression-free survival Among lenvatinib, five 10 TILs. no differences or between groups. Although included only limited number patients, findings suggested that be predicting chemotherapy HCC.

Language: Английский

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MASLD-Related HCC—Update on Pathogenesis and Current Treatment Options

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(4), P. 370 - 370

Published: March 30, 2024

Hepatocellular carcinoma (HCC) is a common complication of chronic liver diseases and remains relevant cause cancer-related mortality worldwide. The global prevalence metabolic dysfunction-associated steatotic disease (MASLD) as risk factor for hepatocarcinogenesis on the rise. Early detection HCC has been crucial in improving survival outcomes patients with steatohepatitis (MASH), even absence cirrhosis. Understanding how develops MASH increasingly becoming current research focus. Additive factors such type 2 diabetes mellitus (T2DM), genetic polymorphisms, intestinal microbiota may have specific impacts. Pathophysiological epidemiological associations between will be discussed this review. We additionally review available tumor therapies concerning their efficacy MASH-associated treatment.

Language: Английский

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Atezolizumab/bevacizumab or lenvatinib in hepatocellular carcinoma: Multicenter real-world study with focus on bleeding and thromboembolic events

JHEP Reports, Journal Year: 2024, Volume and Issue: 6(6), P. 101065 - 101065

Published: April 8, 2024

Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these may be associated the risk of bleeding thromboembolic events. In this study, we evaluated safety focus on events atezo/bev

Language: Английский

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MASLD-Related HCC: A Comprehensive Review of the Trends, Pathophysiology, Tumor Microenvironment, Surveillance, and Treatment Options

Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(6), P. 5965 - 5983

Published: June 13, 2024

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide of metabolic dysfunction-associated steatotic liver disease (MASLD) shift etiology HCC, with MASLD replacing hepatitis B virus as primary contributor new cases HCC. MASLD-related HCC exhibits distinct characteristics compared viral including unique immune cell profiles resulting overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, is frequently identified older age groups among individuals cardiometabolic comorbidities. Additionally, greater percentage occur noncirrhotic patients those etiologies, hindering early detection. However, current clinical practice guidelines lack specific recommendations for screening patients. The evolving landscape management offers spectrum therapeutic options, ranging from surgical interventions locoregional therapies systemic treatments, across various stages disease. Despite ongoing debates, evidence does not support differences optimal treatment modalities based etiology. In this study, we aimed provide comprehensive overview literature trends, characteristics, implications,

Language: Английский

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Immunotherapy in hepatocellular carcinoma: how will it reshape treatment sequencing?

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

The treatment landscape of advanced hepatocellular carcinoma (HCC) has broadened with immune checkpoint inhibitors (ICIs) setting a novel standard care. With the increased number therapies either in first or further line, disentangling possible sequences become much more complex. Yet, all second-line have been evaluated after sorafenib. After ICIs, offering multikinase is widespread approach, shifting forward sorafenib lenvatinib, choosing among regorafenib cabozantinib, already approved refractory setting. Under specific circumstances, ICIs could be maintained beyond disease progression patients proven clinical benefit, as supported by some data emerging from phase III trials immunotherapy HCC. Rechallenge an additional attractive alternative, although requiring careful and individual evaluation efficacy safety such strategy not yet clarified. Still, considerable displays primary resistance to might benefit antiangiogenics alone addition instead. Hopefully, ongoing will enlighten regarding most effective pathways. identification predictive correlates response help allocation at each stage, thus representing urgent matter address HCC research. programmed death ligand 1 expression, tumor mutational burden, microsatellite status being inadequate biomarkers HCC, patient characteristics, drug profile, regulatory approval remain key elements acknowledge routine practice. Despite tissue remaining preferred source, discovery take advantage liquid biopsy overcome availability track changes. Lastly, genetic phenotypes, microenvironment features, gut microbiome, markers systemic inflammation are potential emergent predictors pending validation

Language: Английский

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The evolving role of lenvatinib at the new era of first-line hepatocellular carcinoma treatment

Clinical and Molecular Hepatology, Journal Year: 2023, Volume and Issue: 29(4), P. 909 - 923

Published: May 25, 2023

Emergence of multi-targeted kinase inhibitors (MTIs) and immune checkpoint (ICI) have changed the landscape management in hepatocellular carcinoma (HCC). Combination therapy involving ICI has superseded sorafenib as first-line treatment option for advanced HCC due to their superior response rates survival benefits based on recently published phase III trials. However, role lenvatinib remains uncertain no prospective trials compared its efficacy with HCC. Several retrospective studies shown that may not be inferior combination. Indeed, a growing body evidence suggests is associated outcome non-viral patients, questioning supremacy all patients rendering potential preferred option. Furthermore, high-burden intermediate-stage HCC, accumulating supports lenvatinib, or combination transarterial chemoembolization (TACE), over TACE alone. In this Review, we describe latest surrounding evolving

Language: Английский

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Efficacy of immunotherapy in hepatocellular carcinoma: Does liver disease etiology have a role?

Digestive and Liver Disease, Journal Year: 2023, Volume and Issue: 56(4), P. 579 - 588

Published: Sept. 25, 2023

The systemic treatment of hepatocellular carcinoma (HCC) is changing rapidly. After a decade tyrosine kinase inhibitors (TKIs), as the only therapeutic option for advanced HCC, in last few years several phase III trials demonstrated efficacy immune checkpoint (ICIs). combination anti-PD-L1 atezolizumab and anti-vascular endothelial growth factor (VEGF) bevacizumab superiority over sorafenib currently represents standard care HCC. In addition, durvalumab (an anti-PD-L1) tremelimumab anti-CTLA4) proved to be superior sorafenib, same trial monotherapy showed non-inferiority compared sorafenib. However, early reports suggest an influence HCC etiology modulating response these drugs. particular, lower effectiveness ICIs has been suggested patients with non-viral (in particular non-alcoholic fatty liver disease). Nevertheless, randomized controlled available date have not stratified data suggesting possible impact outcome managed derive from subgroup pre-specified analyses. this review, we aim examine potential on immunotherapy regimens

Language: Английский

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Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Current Strategies and Biomarkers Predicting Response and/or Resistance

Biomedicines, Journal Year: 2023, Volume and Issue: 11(4), P. 1020 - 1020

Published: March 27, 2023

In recent years, immune checkpoint inhibitors (ICIs) have revolutionized the treatment of patients with hepatocellular carcinoma (HCC). Following positive results IMbrave150 trial, combination atezolizumab (an anti-PD-L1 antibody) and bevacizumab anti-VEGF became standard care frontline for advanced stage HCC. Several other trials evaluated immunotherapy in HCC, demonstrating that ICIs-based regimens are currently most effective strategies expanding therapeutic possibilities. Despite unprecedent rates objective tumor response, not all benefit from ICIs. Therefore, order to select appropriate therapy as well correctly allocate medical resources avoid unnecessary treatment-related toxicities, there is great interest identifying predictive biomarkers response or resistance immunotherapy-based regimens. Immune classes genomic signatures, anti-drug antibodies, patient-related factors (e.g., etiology liver disease, gut microbiota diversity) been associated ICIs, but none proposed translated into clinical practice so far. Considering crucial importance this topic, review we aim summarize available data on features HCC immunotherapies.

Language: Английский

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Impact of underlying liver disease on unresectable hepatocellular carcinoma treated with immune checkpoint inhibitors

BJC Reports, Journal Year: 2024, Volume and Issue: 2(1)

Published: Jan. 29, 2024

Immune checkpoint inhibitors (ICIs) are standard therapy for unresectable HCC, but many patients do not respond. Non-viral particularly non-alcoholic steatohepatitis (NASH), have been implicated in ICI resistance.

Language: Английский

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Disease Etiology Impact on Outcomes of Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab: A Real-World, Multicenter Study

Liver Cancer, Journal Year: 2024, Volume and Issue: 13(5), P. 522 - 536

Published: April 10, 2024

The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post hoc analyses IMbrave-150 metanalyses clinical trials PD-1/PD-L1 blockers. As a results, it not clear whether the first-line systemic treatment atezolizumab plus bevacizumab (A + B) equally effective viral nonviral patients.

Language: Английский

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