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1.
Article in Chinese | WPRIM | ID: wpr-907542

ABSTRACT

Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) are important co-inhibitory molecules, while regulatory T cells (Tregs) are important suppressor cells. The increase of them in tumor microenvironment is closely related to tumor immune escape and tumor development. PD-L1 plays an important role in the development and function of Tregs. The application of PD-1/PD-L1 blockade also affects the proliferation and function of Tregs, which further participates in the occurrence of drug resistance and hyperprogressive disease. Further understanding of the role and correlation of PD-L1 and Tregs in tumor immunity and immunotherapy can provide new ideas for improving the efficacy of PD-1/PD-L1 blockade.

2.
Article in Chinese | WPRIM | ID: wpr-906715

ABSTRACT

@#[摘要] PD-1/PD-L1 免疫检查点抑制剂(ICI)在单药或联合治疗肝细胞癌(HCC)的临床试验显示出较好的疗效和安全 性,为其临床应用提供有利的科学依据。单药治疗HCC 的PD-1/PD-L1 ICI 包括纳武利尤单抗(nivolumab)、帕博利珠单抗 (pembrolizumab)和卡瑞利珠单抗(camrelizumab),主要用于肝癌的二线治疗。虽部分HCC 患者可以对PD-1/PD-L1 ICI 单药 治疗产生持久的反应,但总体受益的患者仍然较少。PD-1/D-L1 ICI 联合治疗显示出更好的免疫应答和控制。目前,常用的 联合治疗手段包括与其他类ICI、靶向药物、放疗、化疗以及介入治疗等联合。与双ICI 或ICI 和化疗联合治疗相比,酪氨酸激 酶抑制剂(TKI)和PD-1/PD-L1 ICI 联合治疗显示出更好的疗效。在安全性方面,联合治疗的不良反应发生率发也高于单药 治疗,且更易出现严重或致死性的不良反应。PD-1/PD-L1 ICI 单药和联合治疗HBV/HCV 相关HCC 患者的安全性和有效性 正在研究中,同时接受抗病毒药物治疗患者表现出稳定的治疗应答,但HBV/HCV 病毒重新激活相关的安全性问题,尚未得 出一致结论。

3.
Article in Chinese | WPRIM | ID: wpr-920487

ABSTRACT

@#[摘 要] B7/CD28家族分子作为主要的共信号分子,在T细胞功能调控及免疫应答中发挥着至关重要的作用,关于其功能的研究及应用在世界范围内广泛开展。其中,CD28和CTLA-4都可以与B7-1/B7-2结合,但CD28能够促进T细胞增殖,维持Treg细胞稳态;而CTLA-4则可以抑制T细胞增殖,影响CD4+T细胞的分化;抗CTLA-4单抗ipilimumab与抗PD-1单抗联用能够用于治疗PD-L1+的非小细胞肺癌以及无症状的Ⅳ期黑色素瘤。PD-L1/PD-L2:PD-1途径则可以通过多种方式调节T细胞功能,参与CD8+T细胞“耗竭”状态的形成与维持。目前,针对PD-L1/PD-L2:PD-1途径的免疫治疗相关药物开发广泛且较为成熟,抗PD-1单抗主要通过诱导肿瘤浸润的部分耗竭的CD8+T细胞亚群的扩增发挥抗肿瘤作用。ICOS:ICOSL途径在T细胞分化、细胞因子分泌以及体液免疫应答中起着重要作用,抗ICOS抗体药物feladilimab与抗PD-1单抗联用能够有效治疗多发性或难治性骨髓瘤。B7-H3同时具有共刺激效应和共抑制效应,阻断B7-H3后能够有效增强TIL的抗肿瘤效应,其单抗enoblituzumab能够与抗PD-1单抗联用治疗非小细胞肺癌。B7-H4、人内源性逆转录病毒‑H长末端重复关联蛋白(human endogenous retrovirus‑H long terminal repeat‑associating protein,HHLA)以及含V结构域抑制T细胞活化的免疫球蛋白(V‑domain Ig‑cotaining suppressor of T cell activation,VISTA)均能够提供抑制信号,针对B7-H4靶点的CAR-T治疗以及VISTA的小分子抑制剂CA-170均有临床试验正在进行中。目前,对共信号分子的研究已经获得了长足进展,针对某些活化性分子或者抑制性分子开发了相关抗肿瘤药物并在临床中取得一定成效,但如何进一步提高其治疗有效率、减少不良反应等仍有待探索。

4.
Article in Chinese | WPRIM | ID: wpr-886487

ABSTRACT

@#[摘 要] 骨肉瘤是一种好发于青少年、高度恶性、侵袭性强、易转移的成骨恶性肿瘤。新辅助化疗结合外科治疗使骨肉瘤患者5年生存期超过50%,但针对合并复发和转移的骨肉瘤患者治疗效果仍不理想。免疫治疗被证明是一种行之有效的治疗人类恶性肿瘤的策略。逃避免疫监测被认为是肿瘤恶性进展的主要因素,免疫检查点在调控抗肿瘤免疫效果中发挥重要作用,因此针对这些免疫检查点的阻断剂或抑制剂已成为肿瘤患者有效的治疗手段。本文就近年来PD-1/PD-L1通路抑制剂在难治性骨肉瘤治疗中的作用及机制、临床应用、疗效与安全性等的研究进展进行综述。

5.
China Pharmacy ; (12): 1885-1893, 2021.
Article in Chinese | WPRIM | ID: wpr-886284

ABSTRACT

OBJECTIVE:To provide reference for the selection of more economical programmed death- 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors for National Medical Insurance List and the quality improvement of related economic evaluation. METHODS:Retrieved from CNKI ,VIP,Wanfang database ,PubMed,Web of Science and Ovid Embase ,economic evaluation studies including listed PD- 1/PD-L1 inhibitors of China were collected during the inception to Oct. 2020. CHEERS checklist was used to evaluate the quality of the included literatures ,and the methodological characteristics and economic evaluation results of the included studies were analyzed systematically. RESULTS :A total of 14 literatures were included ,all of which were model-based and with moderate or high quality. However ,there were still some deficiencies in the included literatures ,mainly manifesting as the insufficient reports on the reasons for setting or selecting model parameters ,as well as the great uncertainty of clinical effect data and utility value. Only 3 of the 8 PD-1/PD-L1 inhibitors listed in China were involved in the included literatures. Compared with chemotherapy or targeted therapy plan ,9 literatures(64.29%)showed that the therapy plan containing PD- 1/PD-L1 inhibitors was not cost-effective. CONCLUSIONS :The economic evidence of domestic PD- 1/PD-L1 inhibitors is lacking ,the higher price of imported PD- 1/PD-L1 inhibitors lead to poor economic performance. The existing economic evaluations has some shortcomings in methodological application and parameter selection. Pharmaceutical enterprises should fill in the data gaps and adjust the pricing strategy,researchers should improve the standardization of research ,and medical insurance decision-making departments should improve the judgment on the quality of economic evidences ,so as to promote more economical drugs to be included in the National Medical Insurance List.

6.
Article in Chinese | WPRIM | ID: wpr-876710

ABSTRACT

Objective To explore the dynamic expression of programmed cell death-1 (PD-1) and its ligand PD-L1 at the maternal-fetal interface of mice post-infection with Toxoplasma gondii at early pregnancy and examine its interaction with interferon-γ (IFN-γ). Methods A total of 20 mice at day 0 of pregnancy were randomly assigned into 4 groups, including the 12-day pregnancy control group (12 dpn group), 12-day pregnancy and infection group (12 dpi group), 18-day pregnancy control group (18 dpn group) and 18-day pregnancy and infection group (18 dpi group), respectively. On the 6th day of the pregnancy, mice in the 12 dpi and 18 dpi groups were injected intraperitoneally with 150 tachyzoites of the T. gondii PRU strain, while mice in the 12 dpn and 18 dpn groups were injected with the same volume of PBS. All mice in the four groups were sacrificed on 12th and 18th day of the pregnancy, and the number of placenta and fetus was counted and the weight of placenta and fetus was measured. Then, the placental and uterine tissues of the pregnant mice in each group were sampled for pathological examinations. The mRNA expression of PD-1, PD-L1, T. gondii surface antigen SAG-1 and IFN-γ genes was quantified using a quantitative real-time PCR (qPCR) assay, and the correlation between PD-1 and IFN-γ expression was examined. In addition, the 12 dpn group, 12 dpi group, 18 dpn group, 18 dpi group, PBS negative control of the 12 pdi group and PBS negative control of the 18 dpi group were assigned, and the PD-1 expression was determined in the uterine and placenta tissues of the pregnant mice. Results Adverse pregnant outcomes were seen in mice in the 12 dpi and 18 dpi groups, including placental dysplasia and fetal maldevelopment, and the placental weights and fetal body weights were significantly lower in mice in the 12 dpi and 18 dpi groups than those in the 12 dpn and 18 dpn groups (t = 5.52, 11.44, 12.63 and 11.67, all P < 0.01). The histopathological examinations showed that the decidua and junctional regions of the placental tissues were loosely connected in the 12 dpi and 18 dpi groups, and a large number of inflammatory cells infiltration and congestion were seen in the placental and uterine tissues. qPCR assay detected significant differences in PD-1, PD-L1, IFN-γ and SAG-1 expression in the placental and uterine tissues among the 12 dpn, 12 dpi, 18 dpn and 18 dpi groups (F = 22.48, 51.23, 9.61, 47.49, 16.08, 21.52, 28.66 and 238.90, all P < 0.05), and the PD-1, PD - L1, IFN - γ and SAG - 1 expression was all significantly higher in the placental and uterine tissues of mice in the 12 dpi group than in the 12 dpn group (all P values < 0.05). The PD-1 and PD-L1 expression was significantly lower in the placental tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), and the IFN-γ and SAG-1 expression was significantly higher in the placental and uterine tissues of mice in the 18 dpi group than in the 18 dpn group (all P values < 0.05), while the PD-1 and PD-L1 expression was significantly lower in the placental and uterine tissues of mice in the 18 dpi group than in the 12 dpi group (all P values < 0.05). Immunohistochemical staining showed PD-1 expression in the inflammatory cells of the placental tissues of mice in the 12 dpi group, and no apparent PD-1 expression in the 18 dpi group, while strongly positive PD-1 expression was found in the uterine epithelium of mice in the 12 dpi group, and mildly strong expression was in the 18 dpi group. In addition, the IFN-γ mRNA expression was positively correlated with the PD-1 mRNA expression in placental (rs = 0.99, P < 0.01) and uterine tissues of mice in the 12 dpi group (rs = 0.97, P < 0.01) and in placental (rs = 0.82, P < 0.01) and uterine tissues of mice in the 18 dpi group (rs = 0.81, P < 0.01). Conclusions Following T. gondii infection at early pregnancy, the PD-1 and PD-L1 expression shows a remarkable rise at middle pregnancy and a reduction at late pregnancy in placental and uterine tissues of mice, which appears the same tendency with IFN-γ expression during the same time period, and PD-1 expression positively correlates with IFN-γ expression. The dynamic expression of PD-1 and PD-L1 on the maternal-fetal interface of mice may be mutually mediated by IFN-γ induced by T. gondii infection.

7.
Article in Chinese | WPRIM | ID: wpr-876120

ABSTRACT

@#[Abstract] Objective: To construct and purify the recombinant bispecific antibody (BsAb) targeting PD-1 and CD19 and evaluate its activity. Methods: With pCAR1 plasmid as the vector, the eukaryotic expression vector of anti-PD-1/CD19 BsAb was constructed by molecular cloning technology, and then transfected into mammalian cell line CHO-S by PEI reagent for transiently expressing antibody. The BsAb was purified by Affinity chromatography and then identified by SDS-PAGE and WB. The blocking activity of BsAb on PD-1/PD-L1 in vitro was detected by Luciferase reporter gene assay. The activity of antibody (BsAb)-dependent cell (PBMC)-mediated cytotoxicity (ADCC) in vitro was evaluated by lactate dehydrogenase (LDH) cytotoxicity assay. Results: The double plasmid eukaryotic expression vector pCAR1-19X3 was successfully constructed, and anti-PD-1/CD19 BsAb was successfully expressed in CHO-S cells, named pCAR1-19X3-TY. pCAR1-19X3-TY could effectively block the binding of PD-1 to its ligand PD-L1 in vitro, and the EC50 based on the dose-response curve was 0.306 μg/ml. ADCC results showed that pCAR1-19X3-TY could mediate the cytotoxicity of PBMC against Raji cells, and the curve showed a linear upward trend; when the effect/target ratio was 50∶1, the target cell lysis rate of pCAR1-19X3-TY was (38.9±0.3)%, which was not significantly different from that of the positive treatment group (46.7±4.9)% (P>0.05), but significantly higher than that of the negative control group (1.2±0.1)% (P<0.05). Conclusion: The recombinant anti-PD-1/CD19 BsAb can effectively block the binding of PD-1 and PD-L1 and activate PBMC mediated cytotoxicity against Raji cells. pCAR1-19X3-TY has the potential application value in the treatment of B-cell malignant tumor.

8.
Acta Pharmaceutica Sinica ; (12): 553-556, 2021.
Article in Chinese | WPRIM | ID: wpr-873782

ABSTRACT

(±)-Bicoryanhunine B (1), a new dimeric benzylisoquinoline alkaloid was isolated from the dried tubers of Corydalis yanhusuo by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C18, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, ESI-MS, HR-ESI-MS and 1D/2D NMR. (±)-Bicoryanhunine B (1) was a moderate PD-1/PD-L1 interaction inhibitor with an IC50 value of 7.80 ± 0.49 μmol·L-1. In addition, 1 exhibited potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with an IC50 value of 4.83 ± 2.21 μmol·L-1.

9.
Chinese Journal of Lung Cancer ; (12): 605-612, 2021.
Article in Chinese | WPRIM | ID: wpr-888599

ABSTRACT

BACKGROUND@#Programmed cell death 1 or programmed cell death ligand 1 inhibitor (PD-1/PD-L1 inhibitor) and docetaxel, as the standard second-line treatments of advanced non-small cell lung cancer (NSCLC) patients, have limited effects. There are few studies on whether docetaxel combined with PD-1/PD-L1 inhibitor can increase the efficacy and make patients better benefit. The aim of this study is to evaluate the efficacy and safety of docetaxel combined with PD-1/PD-L1 inhibitor for the second-line treatment of stage IV NSCLC patients.@*METHODS@#Stage IV NSCLC patients (n=118) who received treatment at Shandong Cancer Hospital between October 1, 2018, and December 31, 2020, were retrospectively analyzed. They were divided into observation group (n=69) and control group (n=49) according to different treatment plan. Observation group was given docetaxel plus PD-1/PD-L1 inhibitor, while control group was given PD-1/PD-L1 inhibitor. The clinical curative effect and the incidence of adverse reactions of grade 3 and above were compared between the two groups.@*RESULTS@#The disease control rate (DCR) was higher in the observation group (89.9%) than that in the control group (73.5%) (P=0.019), and the objective response rate (ORR) showed no significant difference between observation group (24.6%) and control group (16.3%) (P=0.276). Till June 22, 2021, the 1-year PFS rate showed no difference between observation group (16.5%) and control group (7.7%) (P=0.205). During the treatment period, the adverse reactions of the two groups were mostly grade 1 to 2, and could be tolerated. The incidence of bone marrow suppression in observation group was higher than that in the control group (P<0.05), and the remaining adverse reactions were not statistically different from control group. Cox regression analysis showed that performance status (PS) (P=0.020) and age (P=0.049) were independent prognostic factors for the effect of docetaxel combined with PD-1/PD-L1 inhibitor.@*CONCLUSIONS@#The second-line treatment with docetaxel plus PD-1/PD-L1 inhibitor in patients with stage IV NSCLC can improve the DCR and prolong the PFS, and the adverse reactions are tolerable.

10.
Chinese Journal of Lung Cancer ; (12): 513-518, 2021.
Article in Chinese | WPRIM | ID: wpr-888592

ABSTRACT

The development of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of cancer patients, but a large population of patients are still ineffective to ICIs treatment or develop aquired drug resistance. In order to improve the clinical benefits, a number of studies on ICIs based combination therapy have been actively explored, and have achieved satisfactory results. With the application of ICIs based combination therapy in clinical practice, increasing attention has been paid to the safety of combination therapy and the management of treatment-related adverse events. In this review, the characteristics of adverse events related to ICIs based combination therapies, especially programmed cell death protein 1/protein ligand 1 (PD-1/PD-L1) inhibitors are discussed, in order to provide profound thoughts for toxicity evaluation and individualized treatment decision in future clinical practice.
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11.
Article in Chinese | WPRIM | ID: wpr-910503

ABSTRACT

Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.

12.
Acta Pharmaceutica Sinica B ; (6): 2299-2312, 2020.
Article in English | WPRIM | ID: wpr-881112

ABSTRACT

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells. In addition, BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumor-infiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs). BBR triggered PD-L1 degradation through ubiquitin (Ub)/proteasome-dependent pathway. Remarkably, BBR selectively bound to the glutamic acid 76 of constitutive photomorphogenic-9 signalosome 5 (CSN5) and inhibited PD-1/PD-L1 axis through its deubiquitination activity, resulting in ubiquitination and degradation of PD-L1. Our data reveals a previously unrecognized antitumor mechanism of BBR, suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.

13.
Chinese Journal of Lung Cancer ; (12): 927-940, 2020.
Article in Chinese | WPRIM | ID: wpr-880214

ABSTRACT

BACKGROUND@#Immune checkpoint inhibitors (ICIs) have good efficacy on most advanced tumors, which brings new hope to patients with advanced tumors. However, the immune system activated by ICIs may attack human normal tissues and organs, resulting in corresponding immunotoxicity, such as checkpoint inhibitor pneumonitis. This article carried out a meta-analysis on the incidence and risk of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand 1 (PD-L1) inhibitor-associated pneumonia in advanced tumors patients.@*METHODS@#The computer retrieval of PubMed, Cochrane Library, EMbase and CNKI was performed, and the studies on the occurrence rate of PD-1/PD-L1 inhibitor-associated pneumonia in terminal cancer patients were collected, with the retrieval time limit of January 2000 to January 2020. Statistical analysis was conducted by using Revman 5.3 and R 3.6.2 software to compare the occurrence rate of pneumonia under different circumstances.@*RESULTS@#15 studies were included, involving 8,642 patients, of which those with PD-1/PD-L1 inhibitor were treatment group, and those with chemotherapy were control group. The odds radio of all grades of immune pneumonia was 6.63, and that of high grade was 4.87. The occurrence rate of all grades of pneumonia in the ICI group with non-small cell lung cancer (NSCLC) was 1.658 times than other tumors, and that of high grade was 2.299 times. The occurrence rate of all grades of pneumonia in second-line or more treatment with ICI was 0.489 times than that in first-line, and that of high grade was 0.449 times than that in first-line or more treatment with ICI.@*CONCLUSIONS@#Compared with chemotherapy, the risk of immune-associated pneumonia is higher in PD-1 and PD-L1 inhibitors, and its occurrence risk is high in the ICI group with NSCLC and the first-line treatment with ICI. This paper provides guidance for clinic treatment of terminal cancers and prevention of complications.

14.
Chinese Journal of Lung Cancer ; (12): 976-982, 2020.
Article in Chinese | WPRIM | ID: wpr-880198

ABSTRACT

Brain metastasis (BM) is a common complication in non-small cell lung cancer (NSCLC), which associates with poor prognosis. Recently, immune checkpoint inhibitors (ICIs) has revolutionized the treatment of tumors. Programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors could produce antitumor effect by activating the autoimmune system. The immunotherapy has already show to have a promising outcome for NSCLC patients with BM, while its specific curative effect and the most ideal mode of the treatment remain to be explored. Here we reviewed the tumor microenvironment (TME) in BM lesions and summarized the role of PD-1/PD-L1 inhibitors in cerebral and its current status in clinical studies.
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15.
Article in Chinese | WPRIM | ID: wpr-843275

ABSTRACT

Programmed death-1 (PD-1) receptor and programmed death-ligand 1 (PD-L1) as a pair of T cell immune response co-stimulatory molecules play a negative role in adoptive immunity by inhibiting T lymphocyte function. Blocking the PD-1/PD-L1 signaling pathway has been a hot spot of research and treatment of cancer. Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer, and there is no approved targeted therapy. Immunotherapy represented by PD-1/PD-L1 blockers, is getting widely studied due to the medical potential of therapy for TNBC. Thereinto, the clinical researches of the monoclonal antibodies against PD-1 or PD-L1 have brought a promising future for the treatment of metastatic TNBC. Currently, there are several trials with anti-PD-1 or anti-PD-L1 monoclonal antibodies and their combination with other therapies in salvage, neoadjuvant, and adjuvant settings on going. In this article, the authors review the current studies about potential value of PD-1/PD-L1 in prognosis, prediction, and treatment in TNBC, intending to cast insight on future basic and clinical studies.

16.
Article in Chinese | WPRIM | ID: wpr-824998

ABSTRACT

@#Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway has been found capable of affecting anti-tumor immune effect in many malignancies in recent years. Patients who are diagnosed with advanced non-small cell lung cancer (NSCLC) have considerable responses after receving inhibitors against PD-1/PD-L1. This paper reviews the clinical progress of PD-1/PD-L1 inhibitors in the treatment of NSCLC.

17.
Article in Chinese | WPRIM | ID: wpr-821916

ABSTRACT

@#[摘 要] 宫颈癌是我国女性常见的恶性肿瘤,其传统治疗方式仍存在较多的毒副作用,在寻求突破治疗宫颈癌的新途径中, 程 序性死亡受体(programmed cell death-1,PD-1)和程序性死亡配体(programmed cell death-ligand 1,PD-L1)是近年来研究较多的抑 制性免疫检查点,其与多种恶性肿瘤的发生、发展和转移有不可分割的联系。PD-1/PD-L1抑制剂在治疗宫颈癌方面,其总体缓解 率为14%~27%,当其联合传统化疗可以更多地提高总体缓解率,目前已有多项相关研究正在进行中。本文对PD-1/PD-L1的生 物学特性及其抗体在宫颈癌治疗中的应用进展作一综述。

18.
Article in Chinese | WPRIM | ID: wpr-821914

ABSTRACT

@#[摘 要] 以PD-1/PD-L1轴为靶点的免疫检查点阻断治疗策略已经应用于临床上多种肿瘤的治疗。PD-L1作为表达于肿瘤细 胞中的重要免疫调控靶点,可以应用单克隆抗体阻断其介导的免疫抑制作用,从而恢复T细胞对肿瘤细胞的识别和杀伤。但是, PD-L1的表达受多种因素调控,包括基因组水平、翻译后修饰过程以及翻译后 CMTM4/6 介导的内含体循环调控等。本文就 PD-L1蛋白表达的受调控过程及其在胶质瘤免疫治疗中作用的研究进展作一综述。

19.
Article in Chinese | WPRIM | ID: wpr-821009

ABSTRACT

@# Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy as comparing with chemotherapy alone for the first-line treatment of advanced NSCLC (non-small lung cancer). Methods: RCTs (randomized controlled trials) on PD-1/PD-L1 inhibitor combined with chemotherapy compared with chemotherapy alone for the first-line treatment of advanced NSCLC were searched in the PubMed, Cochrane Library, EMbase, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), and Chinese Scientific Journal Full-text Database (VIP). RevMan 5.2 software was used for the Meta-analysis. Results: Six RCTs with 3 238 advanced NSCLC patients were included in this study. Meta-analysis showed that the combination therapy group was more effective than the chemotherapy alone group in OS (HR=0.86, 95%CI=0.79~ 0.94, P=0.0006) and PFS (HR=0.81, 95%CI=0.78~0.84, P<0.00001). The incidence of adverse reactions, such as thrombocytopenia of grade 1-5, vomiting, diarrhea, hypothyroidism, hyperthyroidism, rash, pneumonitis, colitis, hepatitis, dysgeusia, hepatitis of grade 3-5 and colitis, in combined treatment group were all higher than those in chemotherapy alone group, the differences were statistically significant (P<0.01 or P<0.05). Conclusions: Compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the OS and PFS of patients with advanced NSCLC in the first-line treatment, while the overall incidence of adverse reactions is higher than chemotherapy.

20.
Article in Chinese | WPRIM | ID: wpr-872829

ABSTRACT

Objective:To clarify the effect of Fangfeng Tongshengtang on early-stage serum endotoxin (ET) and programmed death-1/programmed ligand-1(PD-1/PD-L1) in patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)(early-stage), and exploring the mechanism of Fangfeng Tongshengtang in the treatment of early stage HBV-ACLF. Method:The 69 patients with early stage HBV-ACLF were enrolled in the study and all of them received antiviral drugs, liver protection and jaundice relieving drugs as well as supporting therapy. According to the random number table, 35 patients were randomly assigned to observation group (to take Fangfeng Tongshengtang, and 34 patients were assigned to control group to take placebo. The observation period was 3 weeks in both groups. Before treatment and 1, 2, and 3 weeks after treatment, theserum ET, expression of PD-1/PD-L1 in serum CD4+ and CD8+ T cells, liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total bilirubin (TBIL), and direct bilirubin (DBIL)], coagulation function [prothrombin time (PT), and prothrombin activity (PTA)] were detected to verify the effect of Fangfeng Tongshengtang on HBV-ACLF (early-stage). Result:After 3 weeks of treatment, ET, expression of serum CD4+PD-1+, CD4+PD-L1+, CD8+PD-1+, CD8+PD-L1+, ALT, AST, TBIL, DBIL, and PT decreased significantly (P<0.01), while Alb and PTA increased significantly(P<0.01)in both groups. As compared with the control group, the ET in observation group was lower at 1st, 2nd and 3rd week after treatment (P<0.01), the CD4+PD-1+, CD4+PD-L1+, CD8+PD-1+ and CD8+PD-L1+ in observation group were lower at 2nd week and 3rd week(P<0.05, P<0.01), the ALT, AST, TBIL and DBIL in observation group were lower at 1st, 2nd and 3rd week(P<0.05, P<0.01), the PT in observation group was lower at 2nd and 3rd week(P<0.05), and the PTA in observation group was higher at the 2nd and 3rd week(P<0.01). Conclusion:Fangfeng Tongshengtang can achieve the therapeutic effect for HBV-ACLF (early-stage) probably by reducing the serum ET and the expression of PD-1 / PD-L1 in serum CD4 +, CD8 + T cells.

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