scholarly journals Profile of PD-L1 mRNA Expression in Childhood Acute Leukemia

2021 ◽  
Vol 6 (1) ◽  
pp. 37-41
Author(s):  
Muhammad Al Azhar ◽  
Chainurridha . ◽  
Mururul Aisyi
Keyword(s):  
Mrna Expression ◽  
Internal Control ◽  
Childhood Leukemia ◽  
Immune Checkpoint Inhibitor ◽  
Clinicopathological Features ◽  
Healthy Individuals ◽  
Solid Malignancies ◽  
Programmed Death ◽  
Childhood Acute Leukemia

Background: Programmed Death Ligand 1 (PD-L1) expression was used to determine type of patients who respond to immunotherapy using immune checkpoint inhibitor in several solid malignancies. However, the role of PD-L1 in hematological malignancies is less explored. Therefore, we aim to investigate PD-L1 mRNA expression in childhood leukemia patients. Association between PD-L1 expression and clinicopathological features was also analyzed. Method: Blood samples of 17 childhood leukemia patients and 12 healthy individuals as control were used in this study. The samples were collected in Dharmais Cancer Hospital. Real time PCR was used to analyze PD-L1 expression with GAPDH as internal control. Result: PD-L1 mRNA expression is significantly lower in childhood leukemia patients (medians: 0.0012) compared to healthy individuals (medians: 0.0041) (p=0.017). PD-L1 mRNA expressions were not correlated with age (p=1.000), sex (p=1.000), outcome (p=1.000), type of leukemia (p=1.000), hyperleukocytosis (p=1.000), and syndrome down (p=0.426). Conclusion: PD-L1 expression is lower in leukemia patients compared to healthy controls. PD-L1 expressions were not correlated with all clinicopathological features. Our result provides preliminary data of PD-L1 expression in Indonesian childhood leukemia patients. 

scholarly journals Profile of PD-1 and PD-L1 mRNA Expression in Peripheral Blood of Nasopharyngeal Carcinoma

2020 ◽  
Vol 4 (3) ◽  
pp. 121
Author(s):  
Muhammad Al Al Azhar ◽  
Siti Nadliroh ◽  
Karisma Prameswari ◽  
Handoko Handoko ◽  
Demak Lumban Tobing ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Mrna Expression ◽  
Immune Checkpoint ◽  
Peripheral Blood ◽  
Checkpoint Inhibitors ◽  
Eastern Cooperative Oncology Group ◽  
Healthy Individuals ◽  
Expression Levels ◽  
Programmed Death ◽  
Mrna Expression Levels

Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expression is associated with prognostic and respond to immunotherapy with immune checkpoint inhibitor in several solid malignancies. However, the prognostic roles of PD-1 and PD-L1 expression in nasopharyngeal carcinoma (NPC) are less clear. This study aims to investigate PD-1 and PD-L1 mRNA expression levels in peripheral blood of Indonesian NPC patients and its association with clinicopathological features.Materials and Methods: This study used blood samples of 21 NPC patients and 10 healthy volunteers as controls. Real-time polymerase chain reaction (PCR) was used to measure mRNA expression of PD-1 and PD-L1.Results: PD-1 mRNA expression levels were significantly lower in NPC patients (∆CT mean: 9.65±2.04) compared to healthy individuals (∆CT mean: 8.04±1.51) (p=0.031). In contrast, PD-L1 mRNA expression levels were higher in NPC patients (∆CT mean: 6.96±1.32) compared to healthy individuals (∆CT mean: 7.11±0.55), but the difference was not statistically significant (p=0.554). The expression of PD-1 was associated with tumour-node-metastasis (TNM) stage (p=0.030) but not associated with age (p=1.000), sex (p=1.000), body mass index (p=0.350), tumor stage (p=0.338), nodal stage (p=0.579), metastasis stage (p=0.371), and Eastern Cooperative Oncology Group (ECOG) status (p=0.228). Meanwhile PD-L1 expression was not associated with all clinicophatological features.Conclusion: The PD-1 mRNA expression levels were significantly lower, while PD-L1 expression levels were higher in NPC patients compared to healthy controls. PD-1 expression was correlated with TNM stage.Keywords: nasopharyngeal carcinoma, immune checkpoint inhibitors, PD-1, PD-L1

scholarly journals Modulation of TLR 3, 7 and 8 Expressions in HCV Genotype 3 Infected Individuals: Potential Correlations of Pathogenesis and Spontaneous Clearance

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Rushna Firdaus ◽  
Aritra Biswas ◽  
Kallol Saha ◽  
Anirban Mukherjee ◽  
Falguni Pal ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Internal Control ◽  
Viral Infections ◽  
Hcv Infection ◽  
Spontaneous Clearance ◽  
Therapeutic Approaches ◽  
Genotype 3 ◽  
Mrna Expression Analysis ◽  
Cirrhosis Of Liver

Background. Hepatitis C virus is the major cause of chronic hepatitis worldwide which finally leads to the development of hepatocellular carcinoma. Toll like receptors (TLRs) play an important role in the course of many viral infections, but the role of TLRs in HCV pathogenesis has not been well elucidated so far.Objective. The aim of this study was to analyse the mRNA expression of TLRs 3, 7, and 8 in different stages of HCV infection including chronic, cirrhosis, interferon treated resolved, and relapsed cases.Methodology. Total RNA from whole blood was extracted and mRNA expression of TLRs 3, 7, and 8 genes was analyzed by quantitative real-time RT-PCR usingβ-Actin gene as an internal control.Results. This study consisted of 100 HCV infected individuals and twenty healthy controls. TLR 3 expression was found to be significantly elevated in individuals who had spontaneously cleared the virus(p<0.001), whereas TLR 7 was found to be 3.26 times more elevated in patients with cirrhosis of liver. In IFN induced individuals, TLR 8 expression levels were found to be 2.28-fold elevated as compared to control population.Conclusion. TLRs 3, 7, and 8 are prime biomarker candidates for HCV infection mRNA expression analysis which might improve current therapeutic approaches.

scholarly journals HLA RNAseq reveals high allele-specific variability in mRNA expression

2018 ◽  
Author(s):  
Tiira Johansson ◽  
Dawit A. Yohannes ◽  
Satu Koskela ◽  
Jukka Partanen ◽  
Päivi Saavalainen
Keyword(s):  
Autoimmune Diseases ◽  
Mrna Expression ◽  
Allelic Variation ◽  
Healthy Individuals ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Hla Alleles ◽  
Expression Levels ◽  
Allele Specific

AbstractThe HLA gene complex is the most important, single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. The majority of the studies have focused on the huge allelic variation in these genes; only a few studies have explored differences in expression levels of HLA alleles. To study the expression levels of HLA alleles more systematically we utilised two different RNA sequencing methods. Illumina RNAseq has a high sequencing accuracy and depth but is limited by the short read length, whereas Oxford Nanopore’s technology can sequence long templates, but has a poor accuracy. We studied allelic mRNA levels of HLA class I and II alleles from peripheral blood samples of 50 healthy individuals. The results demonstrate large differences in mRNA expression levels between HLA alleles. The method can be applied to quantitate the expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.Author SummaryEven though HLA is widely studied less is known of its allele-specific expression. Due to the pivotal role of HLA in infection response, autoimmunity, and transplantation biology its expression surely must play a part as well. In hematopoietic stem cell transplantation the challenge often is to find a suitable HLA-matched donor due to the high allelic variation. Classical HLA typing methods do not take into account HLA allele-specific expression. However, differential allelic expression levels could be crucial in finding permissive mismatches in order to save a patient’s life. Additionally, differential HLA expression levels can lead into beneficial impact in viral clearance but also undesirable effects in autoimmune diseases. To study HLA expression we developed a novel RNAseq-based method to systematically characterize allele-specific expression levels of classical HLA genes. We tested our method in a set of 50 healthy individuals and found differential expression levels between HLA alleles as well as interindividual variability at the gene level. Since NGS is already well adopted in HLA research the next step could be to determine HLA allele-specific expression in addition to HLA allelic variation and HLA-disease association studies in various cells, tissues, and diseases.

scholarly journals Immune Checkpoint Inhibitors: A Promising Choice for Endometrial Cancer Patients?

2020 ◽  
Vol 9 (6) ◽  
pp. 1721 ◽  
Author(s):  
Lucia Musacchio ◽  
Serena Maria Boccia ◽  
Giuseppe Caruso ◽  
Giusi Santangelo ◽  
Margherita Fischetti ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Tumor Immune Escape ◽  
Solid Malignancies ◽  
Programmed Death ◽  
Therapy Strategies

Although around 80% of endometrial cancers are diagnosed at early stages and present with a 5-year survival rate exceeding 95%, patients with advanced and recurrent disease show a poor prognosis and low response rates to standard chemotherapy. In the era of targeted therapy, the great advances in the understanding of programmed death-ligand 1 (PD-L1) upregulation in cancer cells, which is responsible for tumor immune escape, have contributed to the increasing interest in immune checkpoint inhibitors as a promising strategy for the treatment of several refractory solid malignancies, including endometrial cancer. Several clinical trials have investigated the efficacy and safety of immune checkpoint inhibitors in endometrial cancer, which already led to the approval of the anti-programmed cell death protein 1 (anti-PD-1) antibody pembrolizumab as a satisfactory alternative for selected patients with unresectable or metastatic disease. As the future of cancer treatment will probably rely on combination therapy strategies, currently, innovative ongoing trials are exploring the potential role of immune checkpoint inhibitors associated with chemotherapy, radiotherapy, and other targeted therapies. Moreover, further research is warranted to discover new specific biomarkers that can accurately predict the response to immunotherapy.

scholarly journals Chronic immune checkpoint inhibitor pneumonitis

2020 ◽  
Vol 8 (1) ◽  
pp. e000840 ◽  
Author(s):  
Jarushka Naidoo ◽  
Tricia R Cottrell ◽  
Evan J Lipson ◽  
Patrick M Forde ◽  
Peter B Illei ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Lung Biopsy ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Total Duration ◽  
Lavage Fluid ◽  
Chest Ct ◽  
Clinicopathological Features ◽  
Programmed Death

BackgroundPneumonitis from immune checkpoint inhibitors (ICI) is a potentially fatal immune-related adverse event (irAE) from antiprogrammed death 1/programmed death ligand 1 immunotherapy. Most cases of ICI pneumonitis improve or resolve with 4–6 weeks of corticosteroid therapy. Herein, we report the incidence, clinicopathological features and management of patients with non-small cell lung cancer (NSCLC) and melanoma who developed chronic ICI pneumonitis that warrants ≥12 weeks of immunosuppression.MethodsPatients with ICI pneumonitis were identified from institutional databases of ICI-treated patients with advanced melanoma and NSCLC between January 2011 and July 2018. ICI pneumonitis was defined as clinical/radiographic evidence of lung inflammation without alternative diagnoses, adjudicated by a multidisciplinary team. Chronic ICI pneumonitis was defined as pneumonitis that persists or worsens with steroid tapering, and necessitates ≥12 weeks of immunosuppression, after ICI discontinuation. Serial chest CT was used to assess radiological features, and tumor response by Response EvaluationCriteria for Solid Tumors V.1.1. Bronchoalveolar lavage fluid (BALF) samples were assessed by cell differential. Lung biopsy samples were evaluated by H&E staining and multiplex immunofluorescence (mIF), where available.ResultsAmong 299 patients, 44 developed ICI pneumonitis (NSCLC: 5/205; melanoma: 1/94), and of these, 6 experienced chronic ICI pneumonitis. The overall incidence of chronic ICI pneumonitis was thus 2%. Of those who developed chronic ICI pneumonitis: the majority had NSCLC (5/6), all sustained disease control from ICIs, and none had other concurrent irAEs. Timing of chronic ICI pneumonitis development was variable (range: 0–50 months), and occurred at a median of 12 months post ICI start. Recrudescence of ICI pneumonitis occurred at a median of 6 weeks after initial steroid start (range: 3–12 weeks), with all patients requiring steroid reintroduction when tapered to ≤10 mg prednisone/equivalent. The median total duration of steroids was 37 weeks (range: 16–43+weeks). Re-emergence of radiographic ICI pneumonitis occurred in the same locations on chest CT, in most cases (5/6). All patients who developed chronic ICI pneumonitis had BALF lymphocytosis on cell differential and organising pneumonia on lung biopsy at initial ICI pneumonitis presentation, with persistent BALF lymphocytosis and brisk CD8+ infiltration on mIF at pneumonitis re-emergence during steroid taper.ConclusionsA subset of patients who develop pneumonitis from ICIs will develop chronic ICI pneumonitis, that warrants long-term immunosuppression of ≥12 weeks, and has distinct clinicopathological features.

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