scholarly journals Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Ritsuzo Kozuka ◽  
Masaru Enomoto ◽  
Minh Phuong Dong ◽  
Hoang Hai ◽  
Le Thi Thanh Thuy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Rank Test ◽  
Baseline Serum ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Chronic Hepatitis B Virus ◽  
Immune Checkpoint Proteins

AbstractSoluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. Pre-treatment sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

scholarly journals Soluble Programmed Cell Death-1 Predicts Hepatocellular Carcinoma Development During Nucleoside Analogue Treatment

2021 ◽  
Author(s):  
Ritsuzo Kozuka ◽  
Masaru Enomoto ◽  
Minh Phuong Dong ◽  
Hoang Hai ◽  
Le Thi Thanh Thuy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Rank Test ◽  
Baseline Serum ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Chronic Hepatitis B Virus ◽  
Immune Checkpoint Proteins

Abstract Soluble immune checkpoint molecules are emerging novel mediators of immune regulation. However, it is unclear whether soluble immune checkpoint proteins affect the development of hepatocellular carcinoma (HCC) during nucleos(t)ide analogue (NA) treatment in patients with chronic hepatitis B virus infection. This study included 122 NA-naïve patients who received NA therapy. We assessed the associations of clinical factors, including soluble immune checkpoint proteins, with HCC development during NA treatment. The baseline serum concentrations of 16 soluble immune checkpoint proteins were measured using multiplexed fluorescent bead-based immunoassay. In total, 13 patients developed HCC during the follow-up period (median duration, 4.3 years). Of the 16 proteins, soluble inducible T-cell co-stimulator (≥ 164.71 pg/mL; p = 0.014), soluble programmed cell death-1 (sPD-1) (≤ 447.27 pg/mL; p = 0.031), soluble CD40 (≤ 493.68 pg/mL; p = 0.032), and soluble herpes virus entry mediator (≤ 2,470.83 pg/mL; p = 0.038) were significantly associated with HCC development (log-rank test). In a multivariate analysis, an sPD-1 level ≤ 447.27 pg/mL (p = 0.014; hazard ratio [HR], 4.537) and α-fetoprotein level ≥ 6.4 ng/mL (p = 0.040; HR, 5.524) were independently and significantly associated with HCC development. sPD-1 is a novel predictive biomarker for HCC development during NA treatment.

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.

Residue Specific Binding Analysis of PD-L1 to Its Monoclonal Antibodies by Computational Alanine Scanning

2021 ◽  
Author(s):  
Wei Wen ◽  
Dading Huang ◽  
Jinxiao Bao ◽  
John Z.H. Zhang
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Monoclonal Antibodies ◽  
Programmed Cell Death ◽  
Cancer Patients ◽  
Specific Binding ◽  
Checkpoint Proteins ◽  
Programmed Cell Death 1 ◽  
Computational Alanine Scanning ◽  
Immune Checkpoint Proteins

Programmed cell death 1 receptor (PD-1) on the surface of T cells and its ligand 1 (PD-L1) are immune checkpoint proteins. Treating cancer patients with inhibitors blocking this checkpoint has...

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 Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

2021 ◽  
Vol 9 (4) ◽  
pp. 778
Author(s):  
Takayuki Murata
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Human Herpesvirus ◽  
Barr Virus ◽  
Programmed Cell Death 1 ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Human Herpesviruses

The immune system has evolved as a complex and efficient means of coping with extrinsic materials, such as pathogens and toxins, as well as intrinsic abnormalities, such as cancers. Although rapid and timely activation of the immune system is obviously important, regulated downregulation of the system is almost as significant as activation to prevent runaway immunity, such as allergies and hypercytokinemia. Therefore, the immune checkpoint programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is beneficial for the host. On the other hand, pathogens have evolved to evade host immunity by taking advantage of the PD-1/PD-L1 pathway. This review is focused on human herpesviruses, such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV), which cause various types of disorders, and their relationships with the PD-1/PD-L1 pathway. Understanding such relationships will be useful for developing preventative and therapeutic methods for disorders caused by herpesviruses.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

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