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 ◽  
...  

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

2019 ◽  
Vol 13 (3) ◽  
pp. 80 ◽  
Author(s):  
Ajoedi Ajoedi ◽  
Muhammad Al Azhar ◽  
Siti Nadliroh ◽  
Sri Hartini ◽  
Rizka Andalusia ◽  
...  

Background: Immunotherapy using immune checkpoint inhibitors has currently emerged as an effective treatment for a subset of colorectal cancer (CRC) patients. The roles of PD-1 and PD-L1 expression levels in peripheral blood to predict patient’s response to immune checkpoint inhibitors are not well established. Therefore, we analyzed PD-1 and PD-L1 mRNA expression levels of peripheral blood in Indonesian CRC patients and explored the association with the clinicopathological features.Methods: Peripheral blood of 25 CRC patients and 10 healthy individuals were collected in Dharmais Hospital-National Cancer Center from 2017 to 2018. PD-1 and PD-L1 mRNA expression levels were analyzed using real time PCR. The associations with clinicopathological variables were analyzed with fisher-exact test or chi square test.Results: PD-1 mRNA expression levels were significantly lower in CRC patients compared to healthy individuals (HI) (mean: 0.0015 ± 0.0013 and 0.017 ± 0.010 respectively, p < 0.001). Although PD-L1 mRNA expression levels were lower in CRC patients, the difference was not statistically significant (mean in CRC and HI: 0.021 ± 0.013 and 0.034 ± 0.028 respectively, p = 0.125). The expression of PD-L1 was higher in CRC females compared to males (p = 0.03). The expression levels of PD-L1 were not associated with different ages (p = 0.673), stages (p = 0.298), histological type of colorectal cancer (p=0.852), patient status (p = 1.000), and body mass index (p = 0.514).Conclusions: The mRNA expression levels of PD-1 and PD-L1 were lower in CRC patients compared to healthy controls. Expression of PD-L1 were correlated with sex, but not correlated with ages, stages, histological type of CRC, patient status, and body mass index.


2018 ◽  
Vol 45 (3) ◽  
pp. 310-319 ◽  
Author(s):  
Smadar Gertel ◽  
Gidi Karmon ◽  
Eszter Szarka ◽  
Ora Shovman ◽  
Esther Houri-Levi ◽  
...  

Objective.Anticitrullinated protein antibodies (ACPA) have major diagnostic significance in rheumatoid arthritis (RA). ACPA are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. The presence of ACPA is associated with joint damage and extraarticular manifestations, suggesting that ACPA may have a significant role in the pathogenesis of RA.Methods.To verify the effect of ACPA on RA-immune cells, peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)–positive patients with RA and healthy controls were cocultured in vitro with ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested whether the stimulatory effects induced by ACPA could be inhibited by the addition of a new multiepitope citrullinated peptide (Cit-ME).Results.We found that ACPA bind specifically to PBMC from CCP-positive patients with RA through the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4- to 13-fold increase) in PBMC derived from CCP-positive patients with RA. Moreover, ACPA upregulated IL-1β and IL-6 mRNA expression levels by 10- and 6-fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA, inhibited the ACPA-induced upregulation of IL-1β and IL-6 by 30%.Conclusion.ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA to decrease their pathogenic effects might provide a novel direction in developing therapeutic strategies for RA.


2016 ◽  
Vol 17 (1) ◽  
pp. 21-32 ◽  
Author(s):  
Sumiko Kobayashi ◽  
Yasunori Ueda ◽  
Yasuhito Nannya ◽  
Hirohiko Shibayama ◽  
Hideto Tamura ◽  
...  

2016 ◽  
Vol 35 (1) ◽  
pp. 63-68 ◽  
Author(s):  
Milena Acimovic ◽  
Snezana Vidakovic ◽  
Natasa Milic ◽  
Katarina Jeremic ◽  
Milos Markovic ◽  
...  

Summary Background: The aim of this study was to investigate the role of peripheral blood markers as additional diagnostic tools to transvaginal ultrasound (TVU) findings in the diagnosis of endometriosis. Methods: This study included 40 patients undergoing laparoscopy for suspected endometriosis from January to December 2012. Preoperative levels of serum CA125, CA19-9, CEA and mRNA expression levels for survivin and VEGF were obtained. Real-time PCR was used to determine relative gene expression. A new diagnostic score was obtained by deploying the peripheral blood markers to the TVU findings. Statistical methods used were Chi-square, Fisher’s, Student’s t-test or the Mann - Whitney test. Results: There was a statistically significant difference in serum CA125, survivin and VEGF levels in patients with endometriosis and those without endometriosis (p<0.001, p=0.025 and p=0.009, respectively). False negative TVU findings were noted in 3/13 patients (23.1%) with peritoneal endometriosis without ovaries involvement. High sensitivity (93.3%), specificity (90.0%), PPV (96.6%), NPV (81.8%) and accuracy (92.5%) were obtained for a diagnostic score based on TVU and significant peripheral blood markers (CA125, survivin and VEGF). Conclusions: Determination of serum CA125, mRNA expression levels for survivin and VEGF along with TVU can contribute to higher accuracy of the noninvasive diagnostic tools for endometriosis.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4673-4673
Author(s):  
Jianyu Weng ◽  
Xin Huang ◽  
Suxia Geng ◽  
Chengwei Luo ◽  
Suijing Wu ◽  
...  

Abstract Abstract 4673 Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. Bone Marrow Stromal Cells (MSCs) are involved in tissue repair and modulating immune responses in vitro and in vivo. MSCs as salvage treatment for refractory cGVHD have been reported in our previous study, however, the possible mechanism have yet not to be determined. Between November 2006 and November 2010, 18 patients were diagnosed with refractory cGVHD, 8 patients were treated with in vitro expanded BM-derived MSCs as a compassionate treatment for refractory cGVHD, 10 patients that did not receive BMSCs treatment were control group. The median MSC dose given was 0.6×106/kg body weight. MSCs were harvested fresh from culture and administered to the patients by intravenous infusions over 30 minutes. The median time of MSC administrations was 3 (range, 2–6). The response was assessed monthly after BMSCs treatment, and the total follow-up period was 6 months. The organ response and the overall response were used to determine the therapeutic efficacies of MSC for refractory cGVHD. The expression of the Jagged2 gene of peripheral blood mononuclear cells in patients at the assessment points were analyzed using the TaqMan real-time polymerase chain reaction, with ABL mRNA expression levels as an internal reference. After BMSCs treatment, a total of 6 patients (75%) had an overall response (PR n=6), and 2 patients had a minor partial response (mPR n=2). The expression levels of Jagged2 mRNA in these cases at the diagnosis of refractory cGVHD were significantly increased, compared with none cGVHD patients (23.94%±18.68% vs 3.76%±1.50%, P < 0.05), and the copies of Jagged2 mRNA in BMSC treatment responsed patients' peripheral blood were significantly reduced (5.15%±3.25%, P <0.05), while Jagged2 mRNA expression levels of the control group were no significant difference (P> 0.05). Our pilot study showed that Jagged2 gene reproduction upregulated when the cGVHD is active, so, dynamic monitoring of Jagged2 mRNA expression may have the potential effect on predicting the activity of chronic graft-versus-host disease. Mechanism of Bone marrow stromal cells to treat refractory cGVHD may be related to down-regulation of donor T cells Notch ligand Jagged2 gene expression, which suppression of T cell Notch signaling pathway activation, thus inducing immune tolerance. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Qing Shao ◽  
Yangyang Wang ◽  
Zhaoyun Liu ◽  
Hui Liu ◽  
Yihao Wang ◽  
...  

Background. Immune-related pancytopenia (IRP) is a kind of autoimmune disease mediated by autoantibodies in bone marrow. T helper 9 (Th9) cell is a new subset of T cell discovered recently, which mainly expresses cytokine interleukin-9 (IL-9) to exert immune function. Th9 cells are associated with a variety of inflammatory diseases, but the role of Th9 cells in IRP remains unclear. Methods. Fifty patients with IRP and 20 healthy controls were enrolled. The percentage of Th9 cells was detected by flow cytometry (FCM) and ELISA. CD4+ lymphocytes were sorted by magnetic beads, and the mRNA expression levels of Th9 cells related transcription factors PU.1 and BATF were detected by RT-PCR. Results. The percentage of Th9 cells in CD3+CD4+ cells was 2.73±1.96% in the untreated group, which was significantly higher than those in the remission group (1.21±0.86%) (p<0.01) and the control group (0.68±0.40%) (p<0.001). And that in the remission group was significantly higher than that in the control group (p<0.05). The level of IL-9 in the untreated group was 183.91±112.42 pg/mL, which was significantly higher than that in the remission group (105.96±64.79 pg/mL) (p<0.01) and control group (56.03±14.49 pg/mL) (p<0.001). That in the remission group was also significantly higher than that in the control group (p<0.01). They were negatively correlated with hemoglobin, red blood cell, white blood cell, and platelet counts and positively correlated with the percentage of CD19+B cells and CD5+CD19+/CD19+B cells, respectively. The mRNA expression levels of PU.1 and BATF in IRP patients were higher than those in controls (p<0.05). Conclusions. The percentage of Th9 cells in the peripheral blood and the level of IL-9 in the serum of patients with IRP were increased, which was related to the severity of the disease.


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