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Objective:To investigate the efficacy and safety of infliximab in the treatment of severe plaque psoriasis and its effect on the expression of programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) in psoriatic lesions.Methods:A total of 17 patients with severe plaque psoriasis were enrolled from Shanghai Skin Disease Hospital from February 2019 to April 2019, and were treated with intravenous drips of infliximab at a dose of 5 mg/kg at weeks 0, 2, 6, 14, 22, 30, 38 and 46. Efficacy was evaluated by using the psoriasis area and severity index (PASI) score at weeks 2, 6, 10, 14, 22, 30, 38, 46 and 52, and adverse events were recorded during the trial. Real-time PCR was performed to determine the expression of PD-1 and PD-L1 in skin tissues of 8 volunteer controls, as well as in skin lesions of 14 patients with plaque psoriasis before treatment and 5 patients with plaque psoriasis after 10-week treatment, and immunofluorescence assay to measure the expression of PD-1 and PD-L1 in skin tissues of 5 volunteers and 5 patients with psoriasis. The independent sample t-test was used to compare the expression of PD-1 and PD-L1 in skin tissues between the patients with plaque psoriasis and controls, and paired t-test to compare the expression of PD-1 and PD-L1 in the skin lesions of patients before and after infliximab treatment. Results:After 2, 6, 10, 14, 22, 30, 38, 46 and 52 weeks of infliximab treatment, the proportion of patients with plaque psoriasis achieving PASI75 was 1/17, 6/16, 9/16, 10/16, 15/15, 14/15, 13/14, 11/13 and 10/11, respectively. Antinuclear antibody staining turned positive in 12 patients, which was the most common adverse reaction, and 1 patient experienced an infusion reaction, which was the most severe adverse reaction. Before the treatment, the expression of PD-1 and PD-L1 (1.111 ± 0.391, 0.902 ± 0.169, respectively) was significantly higher in the skin lesions of patients with psoriasis than in the skin tissues of controls (0.620 ± 0.225, t=3.116, P=0.007; 0.474 ± 0.360, t=3.208, P=0.006, respectively) ; after infliximab treatment, the expression of PD-1 and PD-L1 (0.570 ± 0.230, 0.150 ± 0.050, respectively) in the improved skin lesions was significantly lower than that in the corresponding lesions before the treatment (1.238 ± 0.414, t=3.107, P=0.036; 0.966 ± 0.184, t=8.423, P=0.001, respectively) . Conclusions:Infliximab is effective and safe for the treatment of plaque psoriasis, but monitoring is necessary during treatment. The expression of PD-1 and PD-L1 is aberrantly upregulated in plaque psoriasis lesions, and decreased after infliximab treatment, suggesting that PD-1/PD-L1 may be involved in inflammation regulation in psoriasis.
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Objective To determine the level of soluble B7-H1 (sB7-H1) in serum of patients with colorectal cancer ( CRC) , and to investigate its clinical application value in CRC .Methods 152 cases of CRC, 57 cases of benign colorectal diseases and 59 healthy subjects were enrolled .ELISA was used to determine the sB7-H1 level in serum.The levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 72-4 (CA72-4) were determined by electrochemiluminescence. The level of carbohydrate antigen 50 (CA-50) was determined by chemiluminescence.ROC curve was used to evaluate the diagnostic efficiency of sB 7-H1 alone or combined with other tumor markers in CRC .It also analyzed the correlation between serum sB 7-H1 level and some clinicopathological characteristics including tumor location , depth of invasion , lymph node metastasis status , distant metastasis status and tumor stages.Results (1)The differences of sB7-H1 level among CRC group, colorectal benign disease group and healthy control group ( compared with each other respectively ) were statistically significant ( P<0.001 ) . Levels of CEA, CA19-9, CA72-4 and CA-50 were significantly different between CRC group and benign colorectal disease group ( P<0.05 ) , while there was no significant difference between benign colorectal disease group and healthy control group (P>0.05).(2)The diagnosis ability of sB7-H1, CEA, CA19-9,CA72-4, and CA-50 were determined by the area under curve (AUC), which was 0.730, 0.772, 0.639, 0.663 and 0.635, respectively.The combination of sB7-H1 and CEA showed the best effect , and the AUC reached 0.831.(3)There was no significant correlation between the levels of sB 7-H1 and CEA, or CA19-9, CA72-4, CA-50.(4) Immunohistochemistry result showed that the positive rate of CRC group was 52％, while that of benign disease group was 6.3％.The difference of the positive rate between two groups was statistically significant (P<0.01).And there was a significant correlation between the positive rate of sB 7-H1 level in serum and tumor tissues of CRC patients ( P<0.05 ) .( 5 ) The serum sB7-H1 level in CRC patients was related to lymph node metastasis status (P<0.05).But there was no relationship between sB7-H1 level and other clinicopathological characteristics ( including tumor location , depth of invasion , distant metastasis status and tumor stage ) (P>0.05).Conclusion Serum sB7-H1 has a high clinical application value and could serve as a new tumor marker in CRC .
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Objective To determine the expression of programmed cell death 1 receptor (PDCD 1),its ligands and downstream nuclear factor kappa B (NF-κB) in peripheral blood mononuclear cells (PBMC) of patients with generalized pustular psoriasis (GPP).Methods The total RNA was extracted from 9 GPP patients and 10 healthy controls separately by using Trizol,and reverse transcription PCR (RT-PCR) was performed to determine the mRNA expression of PDCD1,programmed cell death 1 ligand 1 (PD-L1),PD-L2 and NF-κB.Enzyme-linked immunosorbent assay (ELISA) was conducted to the serum levels of interleukin-27 (IL-27),IL-22 and IL-4 in the peripheral blood of 23 GPP patients and 24 healthy controls.Results The mRNA expression of PDCD1 was significantly lower in the GPP group (3.13 ± 4.62) than in the healthy control group (23.70 ± 15.33,t =3.40,P ＜ 0.05).However,the mRNA expression of PD-L1 and PD-L2 was significantly higher in the GPP group than in the healthy control group (PD-LI:[5.70 ± 3.07] × 104 vs.[2.00 ± 1.98] × 104,t =2.96,P ＜ 0.05;PD-L2:[0.95 ± 0.71] × 10-4 vs.[0.16 ± 0.20] × 10-4,t =3.38,P ＜ 0.05).There was no significant difference in the mRNA expression of NF-κB between the GPP group and the healthy control group (P ＞ 0.05).The GPP group also showed significantly higher levels of IL-27,IL-22 and IL-4 compared with the healthy control group (all P ＜ 0.001).Conclusion PDCD1 and its ligands were abnormally expressed in the PBMC of patients with GPP,and may play an important role in the occurrence and development of GPP.
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Objective@#To observe the expression levels of PD-1/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia (CLL) .@*Methods@#The expression of PD-1/PD-L1 in peripheral blood CD8+ T cells, CD4+T cells, CD19+B, and dendrites cells (DC) was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and β2-MG expression were analyzed.@*Results@#①Compared with control, CLL patients, including 39 males and 18 females with the median age of (63.7±10.7) years, had no statistically significant difference in age and gender (P>0.05) . CLL patients had the higher PD-1/PD-L1 expression than healthy controls (P<0.05) . ②In Rai staging, the later the stage, the higher expression of PD-1/PD-L1 (P<0.05) . ③PD-1 expression in CD8+CD38+ group (11 cases) was higher than that in CD8+CD38- group (46 cases) (P=0.004) , and CD8+ poor prognosis chromosome group (14 cases) also had significant higher PD-1 expression than CD8+good prognosis chromosome group (28 cases) (P=0.004) . ④The expression of PD-L1 was higher in CD38+group, ZAP-70+group, and poor prognosis group, as compared to that in CD38-group (P=0.002) , in ZAP-70-group (P<0.001) , in good prognosis group (P=0.023) . There was no correlation between the expression of PD-1/PD-L1 and β2-MG (P>0.05) .@*Conclusion@#This data reveals that PD-1/PD-L1 was highly expressed in CLL patients. Its expression levels were correlated with Rai stage, CD38, ZAP-70, chromosome karyotype, but not with β2-MG. PD-1/PD-L1 may be a prognostic factor in patients with CLL.
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OBJECTIVE: Programmed death-ligand 1 (PD-L1) was expressed in various tumors and antibodies targeting its receptor programmed cell death-1 (PD-1) are emerging cancer therapeutics. This study was designed to evaluate the expression of PD-L1 and its correlation with clinicopathologic features and clinical outcomes in ovarian clear cell carcinoma (OCCC). METHODS: The PD-L1 expression was measured by tissue-microarray-based immunohistochemistry from 122 eligible patients diagnosed with OCCC. The associations of clinicopathologic features with progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier method and multivariate analysis was further performed by Cox regression model. RESULTS: Overall, high PD-L1 expression (PD-L1(high)) was observed in 44.7% (55/123) of OCCC patients, and was strongly associated with advanced stages (p=0.020), positive ascitic fluid (p=0.016), platinum-resistant (PR) disease (p=0.045), and recurrence (p=0.038). Moreover, patients with PD-L1(high) were associated with poorer OS (hazard ratio [HR]=2.877; p=0.001) and PFS (HR=1.843; p=0.021) than those with low PD-L1 expression (PD-L1(low)). In subgroup analysis, PD-L1(high) patients experienced a poorer PFS (HR=1.926; p=0.044) and OS (HR=2.492; p=0.021) than PD-L1(low) cases among advanced stages (III–IV), but this difference was not observed in stage I–II patients. Meanwhile, PD-L1(high) was associated with poorer prognosis than PD-L1(low) in PR patients (OS, HR=2.253; p=0.037; PFS, HR=1.448; p=0.233). Multivariate analysis revealed that PD-L1(high) and advanced stages (III–IV) were adverse independent prognosticators for both PFS (HR(PD-L1)=2.0; p(PD-L1)=0.038; HR(stage)=10.2; p(stage)<0.001) and OS (HR(PD-L1)=3.0; p(PD-L1)=0.011; HR(stage)=14.3; p(stage)<0.001). CONCLUSION: PD-L1(high) might serve as a risk factor for PFS and OS in patients with OCCC. It is possible that immunotherapy targeting PD-L1 pathway could be used in OCCC.
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Humans , Adenocarcinoma, Clear Cell , Antibodies , B7-H1 Antigen , Ascitic Fluid , Disease-Free Survival , Immunohistochemistry , Immunotherapy , Methods , Multivariate Analysis , Ovarian Neoplasms , Prognosis , Recurrence , Risk FactorsABSTRACT
Programmed cell death protein-1/programmed cell death ligand-1 (PD-1/PD-L1) path-way has emerged as a critical target for cancer immunotherapy,and monoclonal antibodies that block either side of this inhibitory interaction have demonstrated impressive activity across a broad set of cancer subtypes.Clinical studies have shown that tumor PD-L1 expression is associated with clinical stages and poor prognosis.Tumor PD-L1 expression detection may help to screen the patients who are most likely to be benefit from anti-PD-1/PD-L1 therapy and evaluate the prognosis.Molecular imaging technology such as PET,SPECT and optical imaging may be the modalities that allowing for noninvasively dynamic detection and overall evaluation of multiple biomarkers.This review focuses on the state of the art of tumor molecular imaging targeting PD-1/PD-L1 pathway.
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Objective To clarify the role of B7-H1 in the immune privilege after corneal transplantation in homogeneity variant mice.Methods We established the experimental animal model of allograft mice by using C57BL/6 mouse as donor and Balb/c mouse as recipient.We allocaated the mice with long time survival (＞50 days) corneal graft into survival group,mice with rejection occurring in 50 days into rejection group,and normal C57BL/6 mice into control group.The transplanted corneal grafts were obtained for future reference at the 8th week after transplantation in survival group,and the time of rejection in rejection group.The expression of B7-H1 mRNA was detected by using immunohistochemistry and real time quantitative PCR (RT-PCR),and the relationship between B7-H1 and the immune privilege after corneal transplantation was analyzed. Results The B7 H1 mRNA was highly expressed in epithelium and endothelium of corneal grafts both in survival and control group,in comparison to an obviously lower expression in rejection group.The relative expression level of B7-H1 mRNA was 200.0 ± 11.5 in survival group,44.7 ± 10.8 in control group,and 6.9 ± 12.0 in rejection group,respectively. There were statistically significant differences among the three groups (F=241.164,P＜0.01 ).The was a significant correlation between the level of B7-H1 mRNA and occurrence rate of rejection in corneal graft (P＜0.01 ).Conclusion The results suggest that the immune privilege after corneal transplantation might be mediated by B7-H1,which plays an important role in maintaining the state of corneal immune privilege.