Immune Checkpoint Inhibitor Can Reduce HCV-RNA without Liver Damage

Fukuda, Ryo; Sugawara, Shunichi; Kondo, Yasuteru

doi:10.2169/internalmedicine.3726-19

Cited by 7 publications

(6 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ICIs-related hepatitis could be critical for patients of hepatocellular carcinoma (HCC) since many HCC patients could have limited liver function due to the liver cirrhosis. Previously, we reported that various kinds of factors including hepatitis B virus, hepatitis C virus, and the HCC microenvironment might affect the immune pathogenesis of liver diseases [18][19][20][21][22][23][24] . In this study, we included 3 HBsAg positive inactive carrier.…”

Section: Discussionmentioning

confidence: 99%

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

Kondo

Akahira

Morosawa

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background and AimsIt has been reported that various kinds of immune checkpoint inhibitors (iCIs) could induce immune-related liver damage. We should focus on the programmed cell death-receptor-1 (PD-1) antibody and non-small cell lung cancer (NSCLC) to analyze the characteristics of hepatitis related to iCIs and find the factors that could be useful biomarkers for the diagnosis. MethodsA single-center retrospective study of 252 NSCLC patients who received PD-1 antibody (nivolumab or pembrolizumab). Some of the biochemical markers and immunological markers were analyzed during PD-1-antibody treatment with or without ALT elevation. Histopathological features were reviewed by a single expert of hepatic pathology focusing on the following features: fibrosis, portal inflammation, lobular inflammation, lobular necrosis. The formation of macro- and micro- granulomas was also evaluated. ResultsThe frequency of liver damage induced by nivolumab including grade 1 to 4 (ALT) was 41.9% (78/186 patients). The positive rate of anti-nuclear antibody in the nivolumab group with iCIs-related hepatitis was significantly higher than that in the nivolumab group without iCIs-related hepatitis (p<0.0001). Granulomatous changes were significantly increased in patients with iCIs-related hepatitis compared with DILI and AIH patients (p<0.05). The ratios of inflammatory cells CD4/CD8, and CD138/CD3 in ICIs-related hepatitis were significantly lower than in those of AIH or DILI patients (p<0.05).ConclusionsWe demonstrated that the pre-existing ANA and characteristic liver histology including CD8+ cells dominancy and granulomatous hepatitis could be biomarkers for the diagnosis of iCIs-related hepatitis in the NSCLC with anti-PD-1 therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

Kondo

Akahira

Morosawa

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although PD-1 is a marker of exhaustion on T cells, it is also a marker of T cell activation. Dysfunctional CD8 + T cells and activated CD8 + T cells up-regulate genes involved in activation of the cell cycle, T cell homing and migration, as well as effector molecules, such as granzymes and co-stimulatory and co-inhibitory receptors [ 60 ]. In fact, the PD-1 high expression on HCV-specific T cells during acute infection do not correlate with the clinical outcome, suggesting that the PD-1 level is marking activation but not exhaustion during acute hepatitis [ 61 ].…”

Section: Pd-1 Modulation For T Cell Exhaustion Reversionmentioning

confidence: 99%

“…HCV-specific CD8 T cells targeting HCV epitopes during persistent infection become exhausted and expresses several negative IC, such as PD-1 [ 18 ]. Different in-vitro studies have shown that the PD-1/PD-L1 blockade can restore T cell reactivity in some patients [ 43 , 72 ] and, there are also clinical evidences that blocking this pathway could lead to HCV control [ 60 , 73 ]. Nevertheless, a bulk of HCV patients are not responders to this immune modulation.…”

Section: Effect Of Pd-1 Modulation and γC-cytokines On Hcv-specifimentioning

confidence: 99%

Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8+ T Cell Response during Chronic Hepatitis C

Peña-Asensio

Calvo

Torralba

et al. 2021

Cells

View full text Add to dashboard Cite

Hepatitis C virus (HCV)-specific CD8+ T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8+ T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.

show abstract

“…A case report published by Fukuda et al (2020) demonstrated a case of HCC with a decline in HCV RNA after administration of anti-PD-1 antibody (nivolumab). HCV-RNA titers decreased, without liver damage, after the initiation of treatment with nivolumab; the decline in HCV RNA titers was observed regardless of the antitumor effect [ 63 ].…”

Section: Immunotherapymentioning

confidence: 99%

Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review

Almeida

Ribeiro

Raposo

et al. 2021

Viruses

View full text Add to dashboard Cite

Immunotherapy has been shown to be highly effective in some types of cancer caused by viruses. Gene therapy involves insertion or modification of a therapeutic gene, to correct for inappropriate gene products that cause/may cause diseases. Both these types of therapy have been used as alternative ways to avoid cancers caused by oncoviruses. In this review, we summarize recent studies on immunotherapy and gene therapy including the topics of oncolytic immunotherapy, immune checkpoint inhibitors, gene replacement, antisense oligonucleotides, RNA interference, clustered regularly interspaced short palindromic repeats Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene editing, transcription activator-like effector nucleases (TALENs) and custom treatment for Epstein–Barr virus, human T-lymphotropic virus 1, hepatitis B virus, human papillomavirus, hepatitis C virus, herpesvirus associated with Kaposi’s sarcoma, Merkel cell polyomavirus, and cytomegalovirus.

show abstract

Immune Checkpoint Inhibitor Can Reduce HCV-RNA without Liver Damage

Cited by 7 publications

References 20 publications

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

Anti-nuclear Antibody and a Granuloma Could be Biomarkers for iCIs-related Hepatitis by Anti- PD-1 Treatment

Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8+ T Cell Response during Chronic Hepatitis C

Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review

Contact Info

Product

Resources

About