Programmed cell death-1 (PD-1) checkpoint blockade in combination with a mammalian target of rapamycin inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1

Hepatology ◽  
2017 ◽  
Vol 66 (6) ◽  
pp. 1920-1933 ◽  
Author(s):  
Hui Li ◽  
Xiaoqiang Li ◽  
Shuang Liu ◽  
Lei Guo ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Hepatoma Cell ◽  
Mammalian Target Of Rapamycin ◽  
Checkpoint Blockade ◽  
Target Of Rapamycin ◽  
Programmed Cell Death 1

scholarly journals Genetic variants of programmed cell death 1 are associated with HBV infection and liver disease progression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Liver Disease ◽  
Programmed Cell Death ◽  
Disease Progression ◽  
Infection Risk ◽  
Hbv Infection ◽  
Liver Disease Progression ◽  
Increased Risk ◽  
Programmed Cell Death 1

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.

scholarly journals Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

2020 ◽  
Vol 14 ◽  
pp. 117955492097636
Author(s):  
Ah-Reum Jeong ◽  
Edward D Ball ◽  
Aaron Michael Goodman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
B Cell ◽  
Solid Tumors ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Checkpoint Blockade ◽  
Programmed Cell Death 1

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.

scholarly journals Evaluation of the Association between Programmed Cell Death-1 Gene Polymorphisms and Hepatocellular Carcinoma Susceptibility in Turkish Subjects. A Pilot Study

2020 ◽  
Author(s):  
Abdullah Fatih Demirci ◽  
Coskun Ozer Demirtas ◽  
Fatih Eren ◽  
Demet Yilmaz ◽  
Caglayan Keklikkiran ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Turkish Population ◽  
Control Group ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Programmed Cell Death 1 ◽  
Significant Difference ◽  
And Control

Background and Aims: Programmed cell death-1 (PD-1) has a vital role in regulating T-cell function, and immune escape mechanism of cancer cells. It was shown that there could be a relationship between single nucleotide polymorphisms (SNPs) in the PD-1 gene and susceptibility to hepatocellular carcinoma (HCC) based on various studies. We aimed to investigate the role of three SNPs within the PD-1 gene in susceptibility to HCC in the Turkish population. Methods: Single nucleotide polymorphisms of PD-1.1, 1.5, and 1.6 were genotyped by using TaqMan Allelic Discrimination Assays in blood samples of 137 HCC and 136 control subjects, matched for age and gender. The genotype, allele and haplotype frequencies were compared in HCC and control groups using logistic regression analysis. Results: Genotype distributions of PD-1.1, PD-1.5 and PD-1.6 SNPs were in Hardy-Weinberg equilibrium. No significant difference was observed in the genotype distribution of PD-1.1, PD-1.5 and PD-1.6 polymorphisms among gender and age-matched HCC (M/F: 96/41; mean age: 61.4 ±11.7 years) and control group (M/F: 94/42; mean age: 61.4±10.1). In the haplotype analysis of PD-1.1/PD-1.5/PD-1.6, no significant difference was found among HCC and control group adjusted for sex and age (all p values>0.1). Conclusion: Our findings, firstly reporting the association of PD-1.5 polymorphism with HCC, and PD-1.1 and PD-1.6 with HCC in the Turkish population, suggest that PD-1 polymorphisms are not predisposing factors for HCC development. Future studies with larger sample sizes and different ethnic populations are required to validate our findings.

scholarly journals A Case of Poorly Differentiated Hepatocellular Carcinoma, Lymphocyte-rich.

2021 ◽  
Author(s):  
Ginji Omori ◽  
Takahiro Osuga ◽  
Koji Miyanishi ◽  
Kota Hamaguchi ◽  
Shingo Tanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Programmed Cell Death 1 ◽  
Poorly Differentiated ◽  
Inhibitor Treatment

A 70-year-old woman was diagnosed poorly differentiated hepatocellular carcinoma (HCC), lymphocyte rich. In this case, programmed cell death 1 expression was observed. Immune checkpoint inhibitor treatment may be effective in such cases, although there have been no reports of their use for poorly differentiated HCC, lymphocyte-rich.

scholarly journals The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Muhammet Ozer ◽  
Andrew George ◽  
Suleyman Yasin Goksu ◽  
Thomas J. George ◽  
Ilyas Sahin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Cell Death ◽  
Liver Cancer ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Primary Liver Cancer ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Line Treatment

The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.

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