PP-049 The immunostaining of programmed death 1 (PD-1) and its ligands in liver tissues of patients with hepatitis and hepatocellular carcinoma

Monocytes (CD14+ cells) from advanced-stage hepatocellular carcinoma (HCC) patients express programmed death 1 ligand (PD-L)/PD-1 and suppress the host antitumor immune response. However, it is unclear whether cancer progression is associated with CD14+ cells. We compared CD14+ cell properties before and after cancer progression in the same HCC patients and examined their role in antitumor immunity. CD14+ cells were isolated from 15 naïve early-stage HCC patients before treatment initiation and after cancer progression to advanced stages. Although CD14+ cells from patients at early HCC stages exhibited antitumor activity in humanized murine chimera, CD14+ cells from the same patients after progression to advanced stages lacked this activity. Moreover, CD14+ cells from early HCC stages scantly expressed PD-L1 and PD-L2 and produced few cytokines, while CD14+ cells from advanced stages showed increased PD-L expression and produced IL-10 and CCL1. CD14+ cells were also isolated from five naïve advanced-stage HCC patients before treatment as well as after treatment-induced tumor regression. The CD14+ cells from patients with advanced-stage HCC expressed PD-L expressions, produced IL-10 and CCL1, and exhibited minimal tumoricidal activity. After treatment-induced tumor regression, CD14+ cells from the same patients did not express PD-Ls, failed to produce cytokines, and recovered tumoricidal activity. These results indicate that PD-L expression as well as CD14+ cell phenotype depend on the tumor stage in HCC patients. PD-L expressions of monocytes may be used as a new marker in the classification of cancer progression in HCC.

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The Efficacy and Safety of Programmed Death-1 and Programmed Death Ligand 1 Inhibitors for the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.626984 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shukang He ◽

Weichao Jiang ◽

Kai Fan ◽

Xiaobei Wang

Keyword(s):

Hepatocellular Carcinoma ◽

Group Treatment ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Efficacy And Safety ◽

Programmed Death Ligand 1 ◽

Programmed Death ◽

Programmed Death 1

BackgroundHepatocellular carcinoma (HCC) is often diagnosed at an advanced stage where only systemic treatment can be offered. The emergence of immune checkpoint inhibitors (ICIs) provides hope for the treatment of HCC. In this study, we performed a meta-analysis to provide evidence for the efficacy and safety of ICIs in the treatment of HCC.MethodsThe following databases and websites were searched: Embase, PubMed, Cochrane Library and ClinicalTrials.gov. The primary endpoints were response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS).ResultsFinally, twelve studies were included in this meta-analysis. When the corresponding outcome indicators and their 95% confidence intervals (CIs) were pooled directly, the overall RR, DCR, PFS and OS were 0.17 (0.15-0.19, I2 = 56.2%, P=0.009), 0.58 (0.55-0.61, I2 = 75.9%, P<0.001), 3.27 months (2.99-3.55, I2 = 73.0%, P=0.001), 11.73 months (10.79-12.67, I2 = 90.3%, P<0.001). Compared to the control group, treatment with ICIs significantly improved RR, PFS and OS, the OR and HRs were 3.11 (2.17-4.44, P<0.001), 0.852 (0.745-0.974, P=0.019) and 0.790 (0.685-0.911, P=0.001), respectively. However, no significant improvement in DCR was found in ICIs treatment in this meta-analysis.ConclusionHCC patients would benefit from ICIs treatment, however, more studies are needed in the future to provide more useful evidence for the treatment of HCC by programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.

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Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using Multiplex Quantitative Analysis

10.21203/rs.3.rs-19039/v2 ◽

2020 ◽

Author(s):

Mengzhou Guo ◽

Feifei Yuan ◽

Feng Qi ◽

Jialei Sun ◽

Qianwen Rao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Tumor Cells ◽

Cd8 T Cells ◽

Prognostic Significance ◽

Normal Liver ◽

Patient Stratification ◽

Programmed Death ◽

Programmed Death 1 ◽

Low Levels

Abstract Background: fibrinogen-like protein 1 (FGL1) - Lymphocyte activating gene 3 (LAG-3) pathway is a promising immunotherapeutic target and has synergistic effect with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1). However, the prognostic significance of FGL1-LAG-3 pathway and the correlation with PD-L1 in hepatocellular carcinoma (HCC) remain unknown.Methods: The levels of LAG-3, FGL1, PD-L1 and cytotoxic T (CD8+T) cells in 143 HCC patients were assessed by multiplex immunofluorescence. Associations between the marker’s expression and clinical significances were studied.Results: We found FGL1 and LAG-3 densities were elevated while PD-L1 and CD8 were decreased in HCC tissues compared to adjacent normal liver tissues. High levels of FGL1 were strongly associated with high densities of LAG-3+cells but not PD-L1. CD8+ T cells densities had positive correlation with PD-L1 levels and negative association with FGL1 expression. Elevated densities of LAG-3+cells and low levels of CD8+ T cells were correlated with poor disease outcome. Moreover, LAG-3+cells deteriorated patient stratification based on the abundance of CD8+ T cells. Patients with positive PD-L1 expression on tumor cells (PD-L1 TC+) tended to have an improved survival than that with negative PD-L1 expression on tumor cells (PD-L1 TC-). Furthermore, PD-L1 TC- in combination with high densities of LAG-3+cells showed the worst prognosis, and PD-L1 TC+ patients with low densities of LAG-3+cells had the best prognosis.Conclusions: LAG-3, FGL1, PD-L1 and CD8 have distinct tissue distribution and relationships with each other. High levels of LAG-3+cells and CD8+ T cells represent unfavorable and favorable prognostic biomarkers for HCC respectively.

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Advanced papillary thyroid carcinoma responding to nivolumab

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220929967 ◽

2020 ◽

pp. 107815522092996

Author(s):

Miguel Michel Ocampo ◽

Jaren Lerner ◽

Shawnt Tosonian ◽

Constantin A Dasanu

Keyword(s):

Hepatocellular Carcinoma ◽

Case Report ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Second Line ◽

Papillary Thyroid ◽

Programmed Death ◽

Programmed Death 1

Introduction Clinical indications of immune checkpoint inhibitors have expanded to a variety of malignancies. Approximately one in six patients with hepatocellular carcinoma respond to programmed death 1 inhibitors nivolumab and pembrolizumab. Case report We report herein a patient with synchronous metastatic hepatocellular carcinoma and advanced papillary thyroid carcinoma treated with nivolumab in the second-line therapy. Management and outcome: The hepatocellular carcinoma showed a durable response to the second-line agent nivolumab. Remarkably, the patient’s papillary thyroid carcinoma also responded to this programmed death 1 inhibitor. Discussion To our knowledge, this is the first case report showing the efficacy of nivolumab in the treatment of metastatic papillary thyroid carcinoma. Further studies with immune checkpoint inhibitors in papillary thyroid carcinoma seem warranted.

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