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1.
Article in Chinese | WPRIM | ID: wpr-1027405

ABSTRACT

Immunotherapy has entered the clinical treatment for various tumors, among which the blockade therapy of PD-1/PD-L1 immune checkpoint is currently the most important tumor immunotherapy method. At present, immunohistochemical method are used in clinical practice to detect PD-L1 expression in tumor patients and screen for indications. However, this method is constrained by factors such as heterogeneity, dynamic changes in PD-L1 expression, and limited sample collection. PD-(L)1 PET imaging utilizes radiolabeled molecules to non-invasively assess PD-(L)1 expression in space and time, and complementary use with IHC has theoretically incomparable advantages. This article reviews the latest progress in the PD-(L)1 probe molecular imaging principles, clinical research and existing problems.

2.
Article in Chinese | WPRIM | ID: wpr-1017868

ABSTRACT

Objective To analyze the therapeutic effect of anti-programmed death receptor 1(PD-1)/pro-grammed death ligand 1(PD-L1)and the characteristics of intestinal flora in patients with non-small cell lung cancer(NSCLC).Methods A total of 81 NSCLC patients admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022 were taken as the research object.According to the patients'immunotherapy response,the patients were divided into non-response group and response group.The differences in clinical data and intestinal flora distribution between the two groups were compared,and the correlation between PFS and intestinal flora a diversity index was analyzed by Spearman correlation.Results The proportion of smoking patients in response group was significantly lower than that in non-re-sponse group,and the difference was statistically significant(x2=4.648,P=0.031).Chao1 index,ACE index and shannon wiener index patients in non-response group were lower than those in response group,while Simpson diversity index was higher than that in response group,with statistical significance(P<0.05).Chao1 index,ACE index and shannon wiener index were positively correlated with PFS(r=0.526,0.579 and 0.539,all P<0.05),while Simpson diversity index was negatively correlated with PFS(r=-0.867,P<0.001).The principal coordinate analysis was used to analyze the β diversity structure of intestinal flora.The first principal component contribution rate was 70.36%,and the second principal component contribution rate was 16.63%.Conclusion The diversity and distribution of intestinal flora in NSCLC patients are related to anti-PD-1/PD-L1 therapy.The higher the diversity of intestinal flora,the more sensitive the anti-PD-1/PD-L1 therapy.

3.
Article in Chinese | WPRIM | ID: wpr-1018021

ABSTRACT

Objective:To prepare the anti-programmed death-ligand 1 (PD-L1) nanoantibody P3C8-C3Fab by ligating with C3Fab and to investigate its role in plasma half-life.Methods:The C3Fab peptide derived from protein G was molecularly fused with the nanobody P3C8 by DNA recombination technology. The nanoantibody P3C8-C3Fab was inducibly expressed and purified in the E. coli BL21 strain, and the binding of it to PD-L1 protein, mouse IgG, and PD-L1-expressing tumor cells was detected by enzyme-linked immunosorbent assay (ELISA). The residual P3C8-C3Fab was detected in mouse serum at different times using double-antibody sandwich ELISA to assess the prolongation of the plasma half-life of PD-L1 nanobodies by C3Fab. Results:The nanoantibody P3C8-C3Fab was successfully constructed, and it could efficiently express itself in soluble form in BL21. The purified NbP3C8-C3Fab protein was obtained with a mass fraction of about 90% at a yield of 7.18 mg/L. The affinity of P3C8-C3Fab for PD-L1 protein and mouse IgG gradually increased with increasing mass concentration and showed a concentration correlation. The binding of P3C8-C3Fab to lung cancer A549 cells showed a concentration correlation. The concentration standard curve of P3C8-C3Fab in mouse serum showed a typical S-shape with a concentration correlation. The plasma half-life of P3C8 was only 0.44 h, while the plasma half-life of P3C8-C3Fab was 21.27-fold higher, up to 9.36 h.Conclusions:The linkage of C3Fab to the nanobodies of P3C8 can significantly prolong the plasma half-life of P3C8, which is valuable for the improvement of in vivo nanobody effects.

4.
Article in Chinese | WPRIM | ID: wpr-1018705

ABSTRACT

Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.

5.
Journal of Clinical Surgery ; (12): 176-181, 2024.
Article in Chinese | WPRIM | ID: wpr-1019314

ABSTRACT

Objective To investigate the clinical effect of transhepatic arterial chemoembolization(TACE)combined with tyrosine kinase inhibitors(TKIs)and programmed death receptors-1(PD-1)inhibitors(TACE+TKIs+PD-1 antibody)in the treatment of moderate advanced unresectable hepatocellular carcinoma(HCC).Methods The clinical data of 65 patients with moderate advanced unresectable hepatocellular carcinoma admitted to the Affiliated Hospital of North Sichuan Medical College from January 2020 to January 2022 were analyzed retrospectively.65 patients were treated with TACE+TKIs+PD-1 antibody.The observation indexes were tumor response,objective response rate(ORR),disease control rate(DCR),total survival time,progression free survival time,conversion operation rate and adverse drug reaction.Results The ORR of 65 p-atients with hepatocellular carcinoma was 49.2%(32/65),and the DCR was 89.2%(58/65).Among them,there were 2 patients with complete remission(CR),30 patients with partial remission(PR),26 patients with stable disease(SD),and 7 patients with progression disease(PD).Among 65 patients with hepatocellular carcinoma,18 patients were transformed into resectable hepatocell-ular carcinoma and underwent RO surgery.The conversion rate was 27.6%(18/65).65 patients were followed up for 3 to 22.4 months,The median follow-up time was 16.5 months.The median overall survival time and median disease progression free survival time of 65 patients were 14.5 months(95%CI:12.3~16.6 months)and 8.8 months(95%CI:6.9~10.6 months),respectively.After treatment,65 patients all had post embolism syndrome(abdominal pain,fever,nausea,vomiting and other symptoms),and some patients had transient abnormal liver function.Adverse drug reactions below grade 3 recovered within a few days.Some patients were associated with multiple adverse drug reactions.1 patient(1.5%)stopped using TACE because of stubborn vomiting,and 5 patients(7.6%)stopped using Lenvatinib because of severe liver function damage during treatment,2 patients(3%)stopped using Camrelizumab because of severe reactive capillary hyperplasia,one patient(1.5%)stopped using Tislelizumab because of severe hypothyroidism,one patient(1.5%)stopped the treatment of Lenvatinib and Sintilimab due to severe gastrointestinal bleeding.The adverse drug reactions of grade 3~4 occurred in other patients were alleviated after drug reduction,symptomatic treatment and hormone treatment.Conclusion TACE+TKIs+PD-1 antibody can obtain reliable clinical efficacy and anti-tumor activity in the treatment of moderate advanced unresectable hepatocellular carcinoma.

6.
Article in Chinese | WPRIM | ID: wpr-1031504

ABSTRACT

ObjectiveTo investigate the possible mechanism of Ruyi Heibai Power (如意黑白散, RHP) in the treatment of vitiligo. MethodsTwenty-four C57BL/6 mice were randomly divided into blank group, model group, high-dose and low-dose RHP groups, with 6 mice in each group. Model group, high- and low-dose RHP groups were all applied hydroquinone to establish vitiligo animal model. After modeling, High- and low-dose RHP groups were given 7.02 g/kg and 2.34 g/kg of RHP by gavage, respectively, while the blank group and model group were intragastrically given 10ml/kg of normal saline, once a day for 36 days. After administration, the skin lesions were observed with naked eye, and HE staining was used to observe the melanin content of the skin lesions. Immunohistochemistry was used to determine the expression of CD3+ and CD8+ T cells in skin tissue. Immunofluorescence staining was used to measure the expression of programmed death receptor 1 (PD-1) in the skin lesion tissue. RT-PCR was used to detect programmed cell death ligand 1 (PD-L1) mRNA expression. ELISA was used to detect serum superoxide dismutase (SOD), tumor necrosis factor (TNF-α), and tyrosinase (TYR) levels. ResultsCompared to those in the blank group, the skin of the mice in the model group was pale, and the melanin content was significantly reduced under the microscope after HE staining; the rate of excellent and good skin lesions decreased, and the melanin granules in the cells around the epidermis and hair follicles decreased significantly; the expression of CD3+ and CD8+ T cells in skin tissue increased significantly, and the expressions of PD-L1 mRNA and PD-1 decreased; the content of TYR decreased, while the content of SOD and TNF-α increased (P<0.05). Compared to those in the model group, the skin color of high- and low-dose RHP groups were deepened, and the melanin content increased; the rate of excellent and good skin lesions increased, as well as the melanin granules in the spinous cell layer, basal cells and hair follicles; the expression of CD3+ and CD8+ T cells in the skin lesions decreased, while PD-L1 mRNA and PD-1 expression increased; the content of TYR increased, while the content of SOD and TNF-α decreased (P<0.05). Compared to the low-dose RHP group, the high-dose group had a larger pigment recovery area in the modeling area, an increased rate of excellent and good skin lesions, an increase in spinous cell layer, basal cells, and hair follicle melanin granules, a decrease in CD3+ and CD8+ T cells expression, an increase in the expression of PD-L1 mRNA and PD-1, an elevated TYR content, and decreased SOD and TNF-α contents (P<0.05). ConclusionRHP can increase skin melanin content of vitiligo mice.The mechanism of action may be related to activating the PD-1/PD-L1 signaling pathway, and then reducing the destruction of melanocytes by T cell-mediated autoimmunity.

7.
Clinics ; Clinics;79: 100395, 2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1564373

ABSTRACT

Abstract Introduction This study aims to explore Programmed Death Receptor-1 (PD-1) and Programmed Death Ligand-1 (PD-L1) variations in Lung Cancer (LC) tissues and Peripheral Blood (PPB) and their association with immunotherapy efficacy and prognosis. Method 72 patients with LC were included in the LC group and 39 patients with concurrent benign lung disease were included in the benign group. PD-1/PDL-1 was compared in PPB and lung tissue. All LC patients were treated with immunotherapy. The relationship between PD-1/PDL-1 in LC tissue and PPB and immunotherapy efficacy was analyzed. Patients were divided into death and survival groups, and PD-1/PDL-1 in tumor tissues and PPB were compared. Results The authors found that PD-1 and PDL-1 positive expression in lung tissue and PPB in LC patients was elevated. Combined detection of PD-1 and PDL-1 was effective in diagnosing LC and evaluating the prognosis of LC patients. PD-1 and PDL-1 positive expression was reduced after disease remission while elevated in dead patients. The 3-year survival rate of patients with PD-1 positive expression was 45.45 % (25/55), which was lower (82.35 %, 14/17) than those with PD-1 negative expression. The 3-year survival rate of patients with positive and negative expression of PDL-1 was 48.78 % (20/41) and 61.29 % (19/31), respectively. Discussion The present results demonstrated that PD-1 and PDL-1 are abnormal in cancer tissue and PPB of LC patients. The combined detection of PD-1 and PDL-1 has diagnostic value for LC and evaluation value for the efficacy and prognosis of immunotherapy.

8.
Cancer Research and Clinic ; (6): 675-679, 2023.
Article in Chinese | WPRIM | ID: wpr-1030354

ABSTRACT

Objective:To investigate the relationship between peripheral blood helper T cell 1/helper T cell 2 (Th1/Th2), helper T cell 17/regulatory T cell (Th17/Treg) and efficacy of programmed death receptor 1 (PD-1) inhibitor in patients with advanced non-small cell lung cancer (NSCLC) combined with chronic obstructive pulmonary disease (COPD).Methods:The clinical data of 107 patients with advanced NSCLC combined with COPD who were admitted to Suzhou Ninth Hospital Affiliated to Soochow University from April 2021 to September 2022 were retrospectively analyzed. The patients were treated with PD-1 inhibitor, and they were categorized into the disease control group (82 cases) and the disease progression group (25 cases) according to the clinical efficacy. Th1/Th2, Th17/Treg and clinical data of patients before treatment were compared between the two groups, and logistic regression was used to analyze the independent influencing factors of patients' PD-1 inhibitor efficacy.Results:Th1/Th2 and Th17/Treg before treatment in the disease control group were higher than those in the disease progression group (12.49±1.14 vs. 7.04±1.06, t = 21.26, P < 0.001; 0.14±0.03 vs. 0.09±0.04, t = 6.72, P < 0.001). The proportions of patients with TNM stage Ⅳ, lymph node metastasis and brain metastasis in the disease progression group were higher than those in the disease control group (all P < 0.01). The results of multivariate logistic regression analysis showed that pre-treatment Th1/Th2 ( OR = 0.744, 95% CI 0.685-0.799, P < 0.001), pre-treatment Th17/Treg ( OR = 0.514, 95% CI 0.465-0.552, P < 0.001), TNM stage ( OR = 1.258, 95% CI 1.049-1.656, P = 0.048), lymph node metastasis ( OR = 1.790, 95% CI 1.223-2.734, P = 0.005), and brain metastasis ( OR = 1.640, 95% CI 1.184-2.348, P = 0.005) were independent influencing factors of PD-1 inhibitor efficacy in patients with advanced NSCLC combined with COPD. Conclusions:Patients with advanced NSCLC combined with COPD who have high Th1/Th2 and Th17/Treg before treatment have good outcomes with PD-1 inhibitor therapy.

9.
Journal of Leukemia & Lymphoma ; (12): 524-527, 2023.
Article in Chinese | WPRIM | ID: wpr-1017351

ABSTRACT

Objective:To investigate the clinical efficacy and side effects of programmed death receptor 1 (PD-1) inhibitor in the treatment of relapsed/refractory non-Hodgkin's lymphoma (NHL).Methods:The clinical data of 31 patients with relapsed/refractory NHL treated with PD-1 inhibitor alone in Linyi Cancer Hospital from July 2018 to December 2021 were retrospectively analyzed. The clinical efficacy and adverse reactions were also analyzed.Results:After 3-4 cycles of PD-1 inhibitor treatment alone, 13 cases achieved partial remission, 3 cases achieved stable disease and 15 cases had the progression of disease. The objective remission rate was 41.9% (13/31), and the disease control rate was 51.6% (16/31). The objective remission rate of patients with peripheral T-cell lymphoma was 42.9% (9/21), and the disease control rate was 57.1% (12/21). By the end of follow-up in July 30, 2022, the median progression-free survival time was 8 months (95% CI 1.6-14.4 months) and the median overall survival time was 15 months (95% CI 5.7-24.3 months). The incidence of adverse reactions in the whole group was 67.7% (21/31), of which grade 1-2 occurred in 20 cases, and grade 3-4 occurred in 1 case. Conclusions:PD-1 inhibitor has a certain effect in the treatment of relapsed/refractory NHL; the overall incidence of adverse drug reactions is high, but they are all controllable.

10.
Journal of Leukemia & Lymphoma ; (12): 701-704, 2023.
Article in Chinese | WPRIM | ID: wpr-1017375

ABSTRACT

Extranodal NK/T cell lymphoma (ENKTCL) is a group of highly aggressive non-Hodgkin lymphoma associated with epstein-barr virus infection. Asparaginase-based chemoradiotherapy regimens are not effective in advanced patients. In recent years, anti-programmed-death receptor 1 (PD-1)/programmed-death receptor ligand 1 (PD-L1) immunotherapy has developed rapidly, which can effectively improve the prognosis of ENKTCL patients. But some patients with ENKTCL still have low response rate. This article reviews the mechanisms of resistance to anti-PD1/PD-L1 therapy and other immune targets in ENKTCL recently to change the traditional treatment mode of ENKTCL through the combination of different targeted drugs.

11.
Chinese Journal of Biologicals ; (12): 105-111+118, 2023.
Article in Chinese | WPRIM | ID: wpr-965587

ABSTRACT

@#Abstract:Programmed death receptor⁃ 1(PD⁃1)belongs to the family of immunoglobulin B7⁃CD28,which plays an important role in regulating immune response in human body. Since the first PD⁃1/PD⁃ligand 1(PD⁃L1)monoclonal antibody was approved for marketing in China in 2018,the value of PD⁃1/PD⁃L1 immunotherapy in oncotherapy has attracted wide attention. Based on the introduction of the action mechanism of PD⁃1/PD⁃L1 mAbs,this paper reviews the application progress of 8 on ⁃ market PD ⁃ 1/PD ⁃ L1 mAbs in China in oncotherapy from the perspectives of approved indications,clinical trials,usage and dosage,and adverse reactions,in order to provide reference for the rational appli⁃ cation of PD⁃1/PD⁃L1 monoclonal antibodies in clinic.

12.
Article in Chinese | WPRIM | ID: wpr-971108

ABSTRACT

OBJECTIVE@#To explore the effect of microRNA-424-5p (miR-424-5p) on the drug resistance of diffuse large B-cell lymphoma (DLBCL) cells by regulating the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling pathway.@*METHODS@#Human DLBCL cell line CRL2631 cells were induced to construct CRL2631-CHOP resistant cell line. RT-qPCR and Western blot were used to detect the expression levels of MiR-424-5p, PD-L1 mRNA and protein, and multidrug resistance gene-1 (MDR-1) protein in CRL2631 cells and CRL2631-CHOP cells, respectively. The target genes of MiR-424-5p was verified by dual luciferase reporter assay. The miRNA simulation/interference technology and thiazole blue (MTT) method were used to detect the resistance of CRL2631 cells and CRL2631-CHOP cells to CHOP.@*RESULTS@#Compared with CRL2631 cells, the drug resistance of CRL2631-CHOP cells to CHOP and the levels of MDR-1 protein (P<0.05), PD-L1 mRNA and protein in the cells were significantly increased (both P<0.001), while the relative level of MiR-424-5p was significantly reduced (P<0.001). The result of the dual luciferase reporter assay showed that PD-L1 was the direct downstream target gene of MiR-424-5p (P<0.001). After transfection of MiR-424-5p inhibitor, the resistance of CRL2631 cells to CHOP drugs increased, and the expression level of MDR-1 protein (P<0.01), PD-L1 mRNA and protein also increased significantly (both P<0.01). After transfection of MiR-424-5p mimics, the resistance of CRL2631-CHOP cells to CHOP drugs decreased, and the expression level of MDR-1 protein (P<0.001), PD-L1 mRNA and protein also decreased significantly (both P<0.001). Overexpression of PD-L1 could reverse the inhibitory effect of upregulating MiR-424-5p on PD-L1 (P<0.001).@*CONCLUSION@#Down-regulation of MiR-424-5p enhances the drug resistance of DLBCL cells by regulating the PD-1/PD-L1 signaling pathway.


Subject(s)
Humans , B7-H1 Antigen/metabolism , Cell Line, Tumor , Drug Resistance , Luciferases , Lymphoma, Large B-Cell, Diffuse/pathology , MicroRNAs/metabolism , Programmed Cell Death 1 Receptor , RNA, Messenger , Signal Transduction
13.
China Pharmacy ; (12): 2256-2262, 2023.
Article in Chinese | WPRIM | ID: wpr-988787

ABSTRACT

OBJECTIVE To evaluate the efficacy and safety of PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer, and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed, Cochrane Library, Embase, American Society of Clinical Oncology Meeting Library, CNKI, VIP and Wanfang database, etc., the randomized controlled trials (RCTs), non-RCT, case-control studies, cohort studies, etc. about PD-1/PD-L1 inhibitors for neoadjuvant treatment of bladder cancer were collected from the inception to Jan 31st, 2023. After literature screening, data extraction and quality evaluation, RevMan 5.3 software was used to perform meta-analysis of single-group rates; sensitivity analysis and publication bias analysis were conducted using Stata12 software. RESULTS A total of 25 studies were included in this discussion, involving 940 patients. The results of meta-analysis showed that the pathologic complete response (pCR) rate was 32% [OR=0.32, 95%CI (0.22, 0.45), P=0.006], downstaging rate was 52% [OR=0.52, 95%CI (0.45, 0.60), P=0.55], and the incidence of ≥grade 3 immune-related adverse events (irAEs) was 16% [OR=0.16, 95%CI (0.11, 0.22), P<0.000 01]. Subgroup analysis showed that the patients receiving PD-1/PD-L1 inhibitors alone had a pCR rate of 25% and a incidence of Grade≥3 irAEs of 9%; the patients receiving combined immunotherapy had a pCR rate of 29% and a incidence of Grade≥3 irAEs of 28%; the patients receiving PD-1/PD-L1 inhibitors combined with chemotherapy had a pCR rate of 43% and a incidence of Grade≥3 irAEs of 12%; PD-L1 positive patients had a pCR rate of 44%, and PD-L1 negative patients had a pCR rate of 25%. The results of the sensitivity analysis showed that the study was robust. The results of the publication bias analysis showed that there was no significant publication bias. CONCLUSIONS PD-1/PD-L1 inhibitors are effective and safe for adjuvant treatment of bladder cancer.

14.
Article in Chinese | WPRIM | ID: wpr-989350

ABSTRACT

Sepsis is currently the leading cause of death in the intensive care unit, and its survivors also experience long-term immunosuppression and high rates of recurrent infections. At present, the clinical treatment of sepsis is still based on antibiotics, intravenous rehydration, and vasopressors, and there is no targeted drug treatment. However, as the rate of antibiotic resistance continues to increase, immunotherapy is highly anticipated as a new treatment. Patients with sepsis are often accompanied by acute leukocyte immune dysfunction and immunosuppression, which may be an important risk factor for the increasing morbidity and mortality of patients. Targeted inhibition of specific cell surface inhibitory immune checkpoint receptors and ligands, such as programmed death receptor-1 (PD-1), programmed death-ligand 1 (PD-L1), and other targets, can improve the host’s resistance to infection. In this paper, the research progress of PD-1 and PD-L1 in the immune response to sepsis was summarized to provide a theoretical basis for their further application in the treatment of sepsis in the future.

15.
Chinese Critical Care Medicine ; (12): 357-361, 2022.
Article in Chinese | WPRIM | ID: wpr-955971

ABSTRACT

Objective:To investigate the effect and mechanism of histone methyltransferase enhancer of zeste homolog 2 (EZH2) on sepsis-induced T cell dysfunction.Methods:Twenty-four male C57BL/6 mice were divided into three groups randomly: sham operated group, sepsis model group [cecum ligation and puncture (CLP)+dimethyl sulfoxide (DMSO) group] and EZH2 selective inhibitor treated group (CLP+GSK126 group), with 8 mice in each group. Sepsis murine model was reproduced by CLP. CLP+DMSO group and CLP+GSK126 group were treated with DMSO or GSK126 (10 mg/kg) respectively right after surgery through intraperitoneal injection. The mice were sacrificed 24 hours after operation, and the mesenteric lymph nodes were collected. The expression of EZH2, apoptosis rates, cell proliferation marker ki-67 antigen positive T lymphocytes (ki-67 + cell), interferon-γ positive T lymphocytes (IFN-γ + cell), programmed death receptor-1 positive T lymphocytes (PD-1 + cell) and programmed death-ligand 1 positive T lymphocytes (PD-L1 + cell) were determined by flow cytometry. Results:Compared with sham operated group, the expression of EZH2 in T lymphocytes was up-regulated on mesenteric lymph nodes of CLP+DMSO group. Compared with CLP+DMSO group, the ratio of CD3 + T lymphocytes in CLP+GSK126 group was up-regulated (0.70±0.02 vs. 0.50±0.07, P < 0.01), indicating that the EZH2 inhibitor could increase the number of T lymphocytes in lymph nodes of septic mice; the ratio of ki-67 + cells in CD4 + and CD8 + T lymphocytes in CLP+GSK126 group was increased (CD4 +: 0.74±0.05 vs. 0.63±0.04, CD8 +: 0.82±0.06 vs. 0.70±0.04, both P < 0.05), indicating that the EZH2 inhibitor could increase the ratio of T lymphocytes with high proliferative activity in lymph nodes of septic mice. However, no significant difference was found on both CD4 + and CD8 + T lymphocytes apoptosis rates in the mesenteric lymph nodes of mice between CLP+GSK126 group and CLP+DMSO group [CD4 +: (21.53±2.87)% vs. (20.48±3.21)%, CD8 +: (8.34±1.02)% vs. (7.71±1.38)%, both P > 0.05], indicating that no extra T lymphocytes apoptosis was induced by EZH2 inhibitor. Compared with CLP+DMSO group, the ratios of IFN-γ + CD4 + and IFN-γ + CD8 + T lymphocytes were increased in CLP+GSK126 group (IFN-γ +CD4 +: 0.31±0.11 vs. 0.14±0.06, IFN-γ +CD8 +: 0.30±0.10 vs. 0.13±0.06, both P < 0.05), suggesting that secretion of IFN-γ in lymph nodes by sepsis T lymphocytes was augmented after EZH2 inhibitor administration. Furthermore, compared with CLP+DMSO group, the ratio of PD-1 + cell in CD8 + T lymphocyte was down-regulated in CLP+GSK126 group (0.092±0.006 vs. 0.135±0.004, P < 0.01), suggesting that EZH2 inhibitor restrained the PD-1 expression on sepsis lymphoid node CD8 + T lymphocytes, however, it had no significant effect on PD-L1 + cells. Conclusion:EZH2, regulates sepsis-induced T lymphocyte dysfunction, possibly through modulating the expression of PD-1.

16.
Cancer Research and Clinic ; (6): 408-412, 2022.
Article in Chinese | WPRIM | ID: wpr-958865

ABSTRACT

Objective:To investigate the relationship between CD8 +FoxP3 +CD25 + T cell subsets and the therapeutic effect of programmed death receptor 1 (PD-1) inhibitor pembrolizumab in treatment of uterine cervical cancer. Methods:The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed. Flow cytometry was used to detect the ratio of CD8 +FoxP3 +CD25 + T cell in peripheral blood of patients. The efficacy and safety were analyzed. According to the efficacy, all patients were divided into remission group (complete remission + partial remission) and non-remission group (stable disease + progressive disease). The clinical characteristics and CD8 +FoxP3 +CD25 + T cell ratio of the two groups were compared. Multivariate logistic regression model was used to analyze the influencing factors for the efficacy. The efficacy of CD8 +FoxP3 +CD25 + T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic (ROC) curve. Results:The objective remission rate of all patients was 17.14% (18/105), and the incidence of adverse reaction was 39.05% (41/105). The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group [5.56% (1/18) vs. 34.48% (30/87)], and the difference was statistically significant ( χ2=6.00, P=0.014). The proportion of CD8 +FoxP3 +CD25 + T cell of 105 patients before and after treatment was (0.83±0.21)% and (0.77±0.10)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the remission group was (0.55±0.26)%, (0.31±0.12)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was (0.89±0.30)%, (0.87±0.28)%, respectively. The proportion of CD8 +FoxP3 +CD25 + T cell after treatment in the remission group was lower than that before treatment ( P < 0.05); there was no statistically significant difference in the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group ( P>0.05). The proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was higher than that in the remission group (all P<0.001). The proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups before treatment and the proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission ( OR=2.542, 95% CI 1.649-3.918, P<0.001; OR=2.936, 95% CI 2.154-4.002, P<0.001). ROC curve analysis showed that the area under the curve of CD8 +FoxP3 +CD25 + T cell ratio predicting the disease remission before treatment was 0.720, and its best cut-off value was 0.77%, the senfitivity was 77.78%, the specificity was 70.11%. Conclusions:Early detection of CD8 +FoxP3 +CD25 + T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.

17.
Article in Chinese | WPRIM | ID: wpr-939688

ABSTRACT

OBJECTIVE@#To investigate the expression of PD-L1 and PD-1 in pathological tissue of patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Data of DLBCL patients who visited the Department of Hematology, Peking University Third Hospital from May 2014 to March 2017 were collected, and a total of 21 patients with pathological tissue sections which were still available at the initial treatment were selected. The patients were divided into complete remission (CR) group and refractory relapse (RR) group according to clinical outcome. The expression and proportion of PD-1 and PD-L1 in pathological tissue sections were detected by multiplex fluorescence immunohistochemical staining, and the differences in the expression of different molecular markers in different clinical characteristics and different prognosis were compared using non-parametric test.@*RESULTS@#The ratio of PD-L1+ cells to PD-1+ cells (PD-L1+ : PD-1+) was 5.14±3.825 in increased lactate dehydrogenase (LDH) group, which was significantly higher than 0.76±0.563 in non-increased LDH group (P=0.001). The ratio of PD-L1+ : PD-1+ in increased Treg cells group was 1.41±1.454, which was lower than 6.42±4.426 in decreased Treg cells group (P=0.023).@*CONCLUSION@#The increased expression ratio of PD-L1 to PD-1 in pathological tissue sections of newly diagnosed DLBCL patients is associated with poor prognostic clinical characteristics.


Subject(s)
Humans , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasm Recurrence, Local , Prognosis , Programmed Cell Death 1 Receptor/metabolism
18.
Article in Chinese | WPRIM | ID: wpr-986475

ABSTRACT

Objective To investigate the expression of PD-1 and PD-L1/2 in T cell subsets and myeloma cells in the bone marrow from newly diagnosed multiple myeloma (NDMM) patients and their relation with clinical features. Methods We collected the bone marrow and clinical data of 22 NDMM patients and 18 cases of healthy controls. We sorted CD4+T cells, CD8+T cells and myeloma cells by flow cytometry, and observed the expression of PD-1 and PD-L1/2. Results Compared with the control group, the proportion of CD8+T cells in the NDMM group was significantly higher, while the ratio of CD4+/CD8+ was significantly lower (both P < 0.05). The expression levels of PD-1 and PD-L2 in CD4+T cells in the NDMM group were significantly higher than those in the control group (both P < 0.05). The expression levels of PD-1, PD-L1 and PD-L2 in T cell subsets and myeloma cells of NDMM patients were not correlated with the gender, age, immune typing, Durie-Salmon stage and subtypes, ISS stage or mSMART3.0 stratification (both P > 0.05). Conclusion Most of MM patients suffering immune abnormality, which may be associated with the mutual immunosuppressive effects between T lymphocytes and plasma cells which expressing PD-1 and PD-L1/2.

19.
Journal of Leukemia & Lymphoma ; (12): 734-737, 2022.
Article in Chinese | WPRIM | ID: wpr-988940

ABSTRACT

Objective:To investigate the effect and safety of rituximab, programmed death 1 (PD-1) monoclonal antibody, and Bruton tyrosine kinase (BTK) inhibitor on elderly refractory primary central nervous system lymphoma (PCNSL).Methods:The clinical data of an elderly patient with refractory PCNSL treated with the combination of rituximab, PD-1 monoclonal antibody and BTK inhibitor in the First Hospital of Jilin University in February 2020 were retrospectively analyzed. The relevant literature was reviewed.Results:The patient had primary central nervous system diffuse large B-cell lymphoma (high-risk group), and the Memorial Sloan Kettering Cancer Center (MSKCC) score was 2 (estimated overall survival time was 7 months). Disease progressed after 1 course of treatment. Complete remission was achieved after the therapy of rituximab, PD-1 monoclonal antibody combined with BTK inhibitor. PD-1 monoclonal antibody maintenance therapy was performed and patient was followed up until November 17, 2021. The patient's condition was stable. The second progression-free survival (PFS) time was 20 months, and the overall survival time was 21 months. The patient well tolerated the new drug treatment, and no adverse reactions of grade 3 or above occurred.Conclusions:The new targeted combination therapy can be used as a treatment option for elderly PCNSL patients, which can further improve the curative effect and significantly improve the prognosis.

20.
Zhongguo fei'ai zazhi (Online) ; Zhongguo fei'ai zazhi (Online);(12): 623-631, 2021.
Article in Chinese | WPRIM | ID: wpr-888601

ABSTRACT

BACKGROUND@#The treatment mode of lung cancer is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for patients with EGFR mutant in non-small cell lung cancer (NSCLC). At the same time programmed death receptor 1 (PD-1) and its programmed death receptor ligand 1 (PD-L1) inhibitors therapy as the representative immune checkpoint inhibitors (ICIs) has a significant effect in the treatment of lung cancer. The aim of this study was to investigate the correlation between the expression of PD-1 and PD-L1 in NSCLC and clinicopathologic feature, EGFR gene mutation.@*METHODS@#The protein expression of PD-1 and PD-L1 was detected by immunohistochemistry from 127 patients with NSCLC and EGFR gene mutation was detected by quantitative polymerase chain reaction (qPCR) to analyze its relation with clinicopathologic feature. Also, the correlation between protein expression of PD-1 and PD-L1 and EGFR mutation.@*RESULTS@#The PD-1 positive expression in NSCLC tumor cells and tumor infiltrating immune cells is 53.5% (68/127), PD-L1 is 57.5% (73/127). The PD-1 and PD-L1 expression significantly higher in well-differentiated and moderately-differentiated carcinoma than poorly differentiated carcinoma, I+II than III+IV in clinical staging (P<0.05). The EGFR mutation rate was 46.5% (59/127), correlate with female, without smoking history, adenocarcinoma and well-differentiated and moderately-differentiated patients respectively higher than male, smoking history, squamous carcinoma and poorly differentiated patients (P<0.05). The protein expression of PD-L1 and PD-1 had the consistency in NSCLC patients (kappa=0.107,5, P=0.487). There was a negative correlation between the EGFR mutation and PD-1 and PD-L1 expression (Φ=-0.209, Φ=-0.221, P<0.05). Follow-up of NSCLC patients, the median total survival in under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, with PD-L1 expression patients respectively higher than over the age of 65, squamous carcinoma, poorly differentiated, without PD-L1 expression patients (P<0.05). The median survival of hypo expression patients of PD-L1 significantly higher than hyper expression patient (P=0.04).@*CONCLUSIONS@#According to the Chinese Expert Consensus on Standards of PD-L1 immunohistochemistry testing for NSCLC, we tested the PD-L1 expression in NSCLC and then the dominant population of anti-PD-1/PD-L1 treatment was screened out. Patients with EGFR mutation were also detected and EGFR mutation was negatively correlated with the expression of PD-1 and PD-L1 as well. On the basis of PD-L1 expression and EGFR mutation status, it may benefit NSCLC patients from individualized treatment. Meanwhile, patients who were under the age of 65, adenocarcinoma, well-differentiated and moderately-differentiated, hypo expression of PD-L1 have a relatively good prognosis, to provide reference for the prognosis evaluation of NSCLC.

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