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| 1 | CCL5/CCR5 axis in human diseases and related treatments显示文摘To defense harmful stimuli or maintain the immune homeostasis, the body produces and recruits a superfamily of cytokines such as interleukins, interferons, chemokines etc. Among them, chemokines act as crucial regulators in defense systems. CCL5/CCR5 combination is known for facilitating inflammatory responses, as well as inducing the adhesion and migration of different T cell subsets in immune responses. In addition, recent studies have shown that the interaction between CCL5 and CCR5 is involved in various pathological processes including inflammation, chronic diseases, cancers as well as the infection of COVID-19. This review focuses on how CCL5/CCR5 axis participates in the pathological processes of different diseases and their relevant signaling pathways for the regulation of the axis. Moreover, we highlighted the gene therapy and chemotherapy studies for treating CCR5-related diseases, including the ongoing clinical trials. The barriers and perspectives for future application and translational research were also summarized. | Zhen Zeng Tianxia Lan Yuquan Wei Xiawei Wei | 2022 | Genes & Diseases2022，9，1： | 12 |
| 2 | Overview of current targeted therapy in gallbladder cancer显示文摘Gallbladder cancer(GBC)is rare,but is the most malignant type of biliary tract tumor.Unfortunately,only a small population of cancer patients is acceptable for the surgical resection,the current effective regimen;thus,the high mortality rate has been static for decades.To substantially circumvent the stagnant scenario,a number of therapeutic approaches owing to the creation of advanced technologic measures(e.g.,next-generation sequencing,transcriptomics,proteomics)have been intensively innovated,which include targeted therapy,immunotherapy,and nanoparticle-based delivery systems.In the current review,we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC.Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease,ultimately improving the efficacy of treatment. | Xiaoling Song Yunping Hu Yongsheng Li Rong Shao Fatao Liu Yingbin Liu | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 3 | 嵌合抗原受体T细胞免疫疗法治疗胰腺癌的研究进展显示文摘胰腺癌是一种高度恶性肿瘤,近年来发病率呈逐年上升趋势。目前还没特别好的筛查、发现和治疗手段,因此迫切需要寻找新的有效安全的胰腺癌治疗方法。近年来,嵌合抗原受体T细胞免疫疗法(chimeric antigen receptor T-cell immunotherapy,CAR-T)在肿瘤方面取得了重大突破,作为目前有效的恶性肿瘤的治疗方式之一,CAR-T细胞治疗效果可持续数年,趋向于长期抗肿瘤记忆,可有效预防复发。该技术进步很快,新的进展几乎以月为单位出现,胰腺癌的根治可能会有实质改善。本文就CAR-T的基本组成、胰腺癌的热门靶点及其面临的主要挑战做出简单的概述,并总结了近期关于CAR-T研究的新进展以及解决问题的方向,为后续治疗胰腺癌提供研究思路。 | 田静 张之勇 白天凯 闫滨 | 2022 | 实用医学杂志2022，38，4： | 6 |
| 4 | The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation显示文摘The immune checkpoint blockade(ICB)targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers.However,the low response rate and frequently observed severe side effects limit its broad benefits.It is partially due to less understanding of the biological regulation of PD-L1.Here,we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation.In PD-L1 and PD-L2 highly expressed cancer cells,a new TAD(topologically associating domain)(chr9:5,400,000-5,600,000)around CD274 and CD273 was discovered,which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2.The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1.After transcription,the PD-L1 is tightly regulated by mi RNAs and RNA-binding proteins via the long 3’UTR.At translational level,PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination.In addition,PD-L1 can be secreted via exosome to systematically inhibit immune response.Therefore,fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy. | Zhiwei Fan Changyue Wu Miaomiao Chen Yongying Jiang Yuanyuan Wu Renfang Mao Yihui Fan | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 4 |
| 5 | The molecular biology of pancreatic adenocarcinoma:translational challenges and clinical perspectives显示文摘Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and incidence.Furthermore,it is usually diagnosed at an advanced stage with a very dismal prognosis.Due to the high heterogeneity,metabolic reprogramming,and dense stromal environment associated with pancreatic cancer,patients benefit little from current conventional therapy.Recent insight into the biology and genetics of pancreatic cancer has supported its molecular classification,thus expanding clinical therapeutic options.In this review,we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and progression.We further discuss potential biomarkers for pancreatic cancer diagnosis,prediction,and surveillance based on novel liquid biopsies.We also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic models.Finally,we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics. | Shun Wang Yan Zheng Feng Yang Le Zhu Xiao-Qiang Zhu Zhe-Fang Wang Xiao-Lin Wu Cheng-Hui Zhou Jia-Yan Yan Bei-Yuan Hu Bo Kong De-Liang Fu Christiane Bruns Yue Zhao Lun-Xiu Qin Qiong-Zhu Dong | 2021 | Signal Transduction and Targeted Therapy2021，6，8： | 1 |
| 6 | 胰腺导管腺癌免疫治疗研究现状和展望显示文摘胰腺导管腺癌(Pancreatic ductal adenocarcinoma, PDAC)是胰腺癌最常见的类型,预后极差。手术切除是目前唯一的根治手段,但多数患者就诊时已失去手术机会。免疫治疗作为一种新兴的治疗手段,在多种实体瘤和血液系统恶性肿瘤治疗中显现出乐观前景。然而,PDAC肿瘤抗原性低以及免疫抑制微环境等特征导致其免疫治疗困难重重。本文通过综述PDAC的肿瘤微环境组成特点和目前开展的新型免疫治疗策略,为PDAC的免疫治疗研究提供新思路。 | 巩芮宁(综述) 任贺(审校) | 2022 | 实用肿瘤学杂志2022，36，6： | 1 |
| 7 | Epithelial cells mimic immune cells: a novel path toward tumor immunotherapy显示文摘Recently,we have shown that FOXP3,a critical transcription factor in regulatory T cells(Tregs),is expressed in pancreatic epithelial cells,and restrain the activity of CD8+T cells by upregulating PD-L1,which in turn regulates immune escape in pancreatic ductal adenocarcinoma(PDAC)^(1).On the basis of a series of studies of our laboratory,we hypothesize that a subset of pancreatic epithelial cells mimics the phenotype and function of Tregs(named quasi-Tregs or qTregs);this concept has been supported by a peer-reviewed commentary^(2).Moreover,evidence suggests that tumor epithelial cells can mimic other types of immune cells and participate in the formation of a tumor immunosuppressive microenvironment(TIM). | Ruining Gong Yan Huang Xiaoxuan Wang Xiaobing Chen Zibin Tian He Ren | 2021 | Cancer Biology & Medicine2021，18，4： | 0 |
| 8 | Targeting chemokines/chemokine receptors:a promising strategy for enhancing the immunotherapy of pancreatic ductal adenocarcinoma显示文摘In recent study published on Nature Medicine,Bockorny et al.1 performed a single-arm phase IIa trial(COMBAT study,NCT02826486)to evaluate safety,efficacy,immunobiological changes,and potential biomarkers for the CXCR4 inhibitor BL-8040,combined with a PD-1 antagonist(pembrolizumab)as a second-line or third-line treatment for patients with metastatic PDAC.This evidence translates the theory of reprogramming tumor immunosuppressive microenvironment into clinical practice and supports that targeting chemokines/chemokine receptors facilitates the immunotherapy of pancreatic ductal adenocarcinoma(Fig.1). | Ruining Gong He Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 9 | Reprogramming immunosuppressive myeloid cells by activated T cells promotes the response to anti-PD-1 therapy in colorectal cancer显示文摘Overcoming local immunosuppression is critical for immunotherapy to produce robust anti-tumor responses.Myeloid-derived suppressor cells(MDSCS)are key regulators of immunosuppressive networks and promote tumor progression.However,it remains unclear whether and how tumor-infltrating MDSCS are shaped in response to anti-PD-1 treatment and what their impact on therapeutic efficacy is in colorectal cancer(CRC).In this study,the levels of infltrating MDSCS were significantly higher in the non-responding organoids and were selectively reduced in the responding group,with MDSCS showing increased apoptosis and attenuated functional activity after anti-PD-1 treatment.A negative correlation between T-cell activation and MDSC function was also observed in fresh human CRC tissues.Mechanistic studies revealed that autocrine IFN-α/B upregulated TRAIL expression on activated T cells to elicit MDSC apoptosis via the TRAIL-DR5 interaction and acted synergistically with TNF-α to inhibit MDSC function of suppressing the T-cell response through the JNK NMDAR-ARG-1 pathway.Moreover,blockade of IFNa/βand TNF-α abolished the therapeutic efficacy of anti-PD-1 treatment by preserving the frequency and suppressive activity of infltrating MDSCS in a CRC mouse model.This result suggested that reprogramming MDSCS by IFN-α/βand TNF-α from activated T cells was necessary for succesful anti-PD-1 treatment and might serve as a novel strategy to improve the response and efficacy of anticancer therapy. | Jing Chen Hong-Wei Sun Yan-Yan Yang Hai-Tian Chen Xing Juan Yu Wen Chao Wu Yi-Tuo Xu LiLian Jin Xiao-Jun Wu Jing Xu Limin Zheng | 2021 | Signal Transduction and Targeted Therapy2021，6，2： | 0 |
| 10 | 胰腺癌免疫治疗研究进展显示文摘胰腺癌作为一种致命的恶性肿瘤,起病隐匿,对放化疗、靶向治疗等传统治疗不敏感,患者预后极差。免疫治疗是当今多种恶性肿瘤综合治疗的有效手段,以其显著临床疗效而备受瞩目。然而胰腺癌因其较低的肿瘤免疫原性和独特的肿瘤微环境在免疫治疗迅速发展的当今成为难以攻破的一方“免疫荒漠”。目前胰腺癌免疫治疗的研究方向主要包括:肿瘤疫苗、免疫检查点抑制剂、单克隆抗体、溶瘤病毒、T细胞治疗等。本文将对以上相关研究进展作一综述,以期为胰腺癌的免疫治疗提供新思路。 | 朱玉兰 郑晓 陈陆俊 | 2023 | 临床肿瘤学杂志2023，28，6： | 0 |
| 11 | 吉西他滨化疗联合PD-1/PD-L1阻断治疗胰腺导管腺癌的研究进展显示文摘胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)不仅对于PD-1/PD-L1阻断剂单药治疗无效,而且对于常用的吉西他滨化疗也产生了耐药性,原因可能是PDAC具有独特的肿瘤微环境。目前,已有相关研究报道吉西他滨加抗PD-1抗体治疗延长了PDAC肝转移小鼠模型的生存期。全文综述PDAC对吉西他滨治疗产生耐药性的机制,并且探讨了抗PD-1/PD-L1抗体联合吉西他滨治疗PDAC可改善患者生存期的可能性。 | 李立群 杨晓军 全赢 侯孟森 赵永忠 | 2023 | 肿瘤学杂志2023，29，11： | 0 |
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