Review
Immunology
Rongping Chen, Lixin Zhou
Summary: Sepsis, one of the leading causes of death in ICU patients, has shown promising treatment potential with anti-PD-1/PD-L1 antibodies due to the important role of the PD-1 signaling pathway in the disease. The relationship between the PD-1 signaling pathway and immune cells as well as organ dysfunction in sepsis has been widely studied, emphasizing the potential application of the PD-1 signaling pathway in sepsis treatment.
CLINICAL IMMUNOLOGY
(2021)
Review
Immunology
Shubai Zhong, Yuanqin Yin
Summary: Sepsis is a severe syndrome with high incidence and mortality that occurs when the immune system overreacts to an infection, leading to multiple organ dysfunction. Immunosuppression plays a crucial role in the clinical treatment and prognosis of sepsis. Recent studies have highlighted the involvement of the programmed cell death 1 signaling pathway in the development of immunosuppression in sepsis. This review systematically presents the mechanisms of immune dysregulation in sepsis, discusses the expression and regulatory effects of the programmed cell death 1 signaling pathway on immune cells associated with sepsis, and explores the current research developments and prospects for using this pathway in immunomodulatory therapy for sepsis. The review also identifies remaining questions and future research directions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
JiaYu Chang, XuQuan Jing, Ying Hua, KaiXing Geng, RuYue Li, ShuangQing Lu, Hui Zhu, Yan Zhang
Summary: This study retrospectively evaluated the safety and efficacy of immune checkpoint inhibitors in small cell lung cancer patients with brain metastases. The results showed that chemotherapy, radiotherapy, and at least four cycles of immunotherapy improved overall survival and intracranial progression-free survival in these patients.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Oncology
Keiichiro Mori, Benjamin Pradere, Fahad Quhal, Satoshi Katayama, Hadi Mostafaei, Ekaterina Laukhtina, Victor M. Schuettfort, David D'Andrea, Shin Egawa, Karim Bensalah, Manuela Schmidinger, Thomas Powles, Shahrokh F. Shariat
Summary: The study found that compared to sunitinib, anti-PD-1 combination therapy in mRCC patients is associated with better overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and complete response rates (CRR). Network meta-analysis indicated that pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy.
CANCER TREATMENT REVIEWS
(2021)
Review
Medicine, General & Internal
Jingyi Zhang, Kexin Tan, Xuejiao Jiang, Shuyue Zheng, Jia Li, Chongxiang Xue, Xu Zhang, Huijuan Cui
Summary: Through meta-analysis, it was found that pseudoprogressive disease caused by PD-1/PD-L1 inhibitors is not common, but close monitoring and proper management should be carried out in clinical practice.
Review
Gastroenterology & Hepatology
Lin-Lin Zheng, Chang-Cheng Tao, Zong-Gui Tao, Kai Zhang, An-Ke Wu, Jian-Xiong Wu, Wei-Qi Rong
Summary: Recent years have seen success in phase III trials for targeted therapeutic agents in treating advanced hepatocellular carcinoma (HCC), with immunotherapy also considered effective. However, treating advanced HCC remains a challenge, highlighting the urgent need for new treatments.
WORLD JOURNAL OF GASTROINTESTINAL SURGERY
(2021)
Article
Gastroenterology & Hepatology
Lin-Yan Zhou, Ying Xie, Yan Li
Summary: Bifidobacterium infantis can regulate the immune response by activating the PD-1/PD-L1 pathway, promoting the proliferation of T cells and regulating the expression of Foxp3.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Review
Oncology
Chao Cheng, Lingdun Zhuge, Xin Xiao, Siyuan Luan, Yong Yuan
Summary: As the predominant treatment option for advanced esophageal cancer, PD-1 and PD-L1 inhibitors provide new hope to clinical practice. However, some patients do not respond to this therapy and most initially sensitive patients eventually develop resistance. Therefore, it is critical to understand the mechanisms of resistance and explore efficient strategies to overcome it, in order to expand the benefit of immunotherapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Zaishang Li, Xueying Li, Wayne Lam, Yabing Cao, Hui Han, Xueqi Zhang, Jiequn Fang, Kefeng Xiao, Fangjian Zhou
Summary: Comparing anti-PD-1 and anti-PD-L1 therapies in platinum-resistant UC patients reveals that anti-PD-1 therapy exhibits better antitumor activity, with comparable safety profiles and survival outcomes. This systematic comparison may enhance treatment awareness in this patient population.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Chunyi Shen, Zhen Zhang, Yonggui Tian, Feng Li, Lingxiao Zhou, Wenyi Jiang, Li Yang, Bin Zhang, Liping Wang, Yi Zhang
Summary: The study demonstrated that combining SFN with CAR-T cells enhanced cytotoxicity and antitumor functions by modulating the PD-1/PD-L1 pathway, suggesting a promising strategy for cancer immunotherapy.
Article
Oncology
Topias Karjula, Hanna Elomaa, Anne Niskakangas, Olli Mustonen, Iiris Puro, Teijo Kuopio, Maarit Ahtiainen, Jukka-Pekka Mecklin, Toni T. Seppala, Erkki-Ville Wirta, Eero Sihvo, Juha P. Vayrynen, Fredrik Yannopoulos, Olli Helminen
Summary: The study found that CD3(+) and CD8(+) T-cell density and PD-1/PD-L1 expression have prognostic value in pulmonary metastases of colorectal cancer. T-cell infiltration is higher in pulmonary metastases compared to primary tumors. High CD3(+) and CD8(+) cell density are associated with better survival, while high PD-L1 expression is associated with favorable prognosis.
Article
Biochemistry & Molecular Biology
Chen Ma, Yi Zhang, Jin'e Lei, Jing Zhang, Fang Li, Xiaqin He, Jing Yuan, Wen Li, Wei Chen
Summary: The study aimed to investigate the resistance and biofilm formation characteristics of pneumococcal meningitis (PM) and the mechanism of programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) signaling pathway (SPW). It was found that streptococcus pneumoniae had multidrug resistance, and the thickness of biofilm decreased with the increase of penicillin minimum inhibitory concentration (MIC). Blocking the PD-1/PD-L1 pathway improved the symptoms of PM.
CELLULAR AND MOLECULAR BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Yuanyuan Wu, Hongbing Wang, Dongdong Wei
Summary: This study reveals that MAGT1 enhances the growth and radioresistance of glioma cells by modulating the ERK/MAPK signaling pathway and upregulating PD-L1 expression.
Article
Oncology
Yingying Wang, Lu Meng, Shuyan Meng, Litang Huang, Shilan Luo, Xiaoting Wu, Xiaomei Gong
Summary: Radiation resistance in NSCLC can lead to recurrence and metastasis after radiotherapy. Immune subversion is a major cause of radiation resistance. While previous research has identified PD-L1 as a factor in radiation resistance, it is not a reliable predictor of radiotherapy efficacy. This study explored the role of FLOT1 in radiation resistance and found that it positively regulates PD-L1, promotes DNA damage and tumor regression, and activates the STING signaling pathway to trigger an antitumor immune response. These findings suggest that FLOT1 could be a promising biomarker and therapeutic target for enhancing radiotherapy effects in NSCLC.
CANCER BIOLOGY & THERAPY
(2023)
Review
Medicine, General & Internal
Chu-Ling Li, Yong Song
Summary: Immunotherapy has greatly impacted the treatment of non-small cell lung cancer, with combination strategies showing promising clinical outcomes. However, there is still room for improvement in response rates, necessitating exploration of alternative combination models and candidate selection strategies.
CHINESE MEDICAL JOURNAL
(2021)
Article
Chemistry, Medicinal
Kuojun Zhang, Yiwu Yao, Zhengchao Tu, Chenzhong Liao, Zhen Wang, Yatao Qiu, Dong Chen, Dale J. Hamilton, Zheng Li, Sheng Jiang
FUTURE MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Organic
Shang Jiang, Xinrui Dong, Yatao Qiu, Dong Chen, Xiaoxing Wu, Sheng Jiang
TETRAHEDRON LETTERS
(2020)
Review
Chemistry, Medicinal
Minmin Wang, Tianyu Wang, Xiangyu Zhang, Xiaoxing Wu, Sheng Jiang
FUTURE MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Qicai Xiao, Huirong Lin, Juan Wu, Xin Pang, Quanming Zhou, Yue Jiang, Pan Wang, Wingnang Leung, Hungkay Lee, Sheng Jiang, Shao Q. Yao, Liqian Gao, Gang Liu, Chuanshan Xu
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Kuojun Zhang, Zhiyi Liu, Yiwu Yao, Yatao Qiu, Feng Li, Dong Chen, Dale J. Hamilton, Zheng Li, Sheng Jiang
Summary: This study reports a novel near-infrared imaging probe for TNBC detection by visualizing class I HDACs, with the potential to improve TNBC diagnosis and treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tianyu Wang, Shi Cai, Mingming Wang, Wanheng Zhang, Kuojun Zhang, Dong Chen, Zheng Li, Sheng Jiang
Summary: This study reports the design, synthesis, and evaluation of a series of biphenyl pyridines as inhibitors of the PD-1/PD-L1 axis. Compound 24 was found to effectively inhibit the interaction between PD-1 and PD-L1, enhance immune cell killing of tumor cells, and demonstrate significant in vivo antitumor activity in a mouse model. The results suggest that compound 24 is a promising small-molecule inhibitor against the PD-1/PD-L1 axis and warrants further development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tianyu Wang, Shi Cai, Yao Cheng, Wanheng Zhang, Minmin Wang, Huiyong Sun, Binghua Guo, Zheng Li, Yibei Xiao, Sheng Jiang
Summary: Compound 17 is a bifunctional inhibitor that can block the interactions between PD-1 and PD-L1, promoting internalization and degradation of PD-L1. It effectively suppresses tumor growth in vivo by activating antitumor immunity.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Lu Lu, Zhihao Qi, Tianyu Wang, Xiangyu Zhang, Kuojun Zhang, Kaizhen Wang, Yao Cheng, Yibei Xiao, Zheng Li, Sheng Jiang
Summary: Several novel benzamide derivatives were synthesized and evaluated for their inhibitory activity against PD-1/PD-L1 interaction. Compound D2 showed better potency than BMS202 and efficiently activated anti-tumor immunity. The results suggest that D2 is a promising lead compound for further development.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Medicinal
Kaizhen Wang, Kuojun Zhang, Xiangyu Zhang, Dong Chen, Sheng Jiang
Summary: Metformin, an oral hypoglycemic drug, is widely used as the first-line treatment for type 2 diabetes mellitus due to its high efficacy and low cost. Recently, it has gained attention for its newly discovered anti-tumor effect, particularly in hepatocellular carcinoma. This article reviews the latest research findings on the mechanisms by which metformin acts against hepatocellular carcinoma, as well as related preclinical trials and the potential limitations and future directions of its use in the treatment of hepatocellular carcinoma.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Lixin Zhou, Tianyu Wang, Kuojun Zhang, Xiangyu Zhang, Sheng Jiang
Summary: Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine protein kinase that negatively regulates T cells, B cells, and dendritic cells-mediated immune responses. It plays a role in cellular processes such as immune cell activation, differentiation, proliferation, adhesion, and apoptosis. HPK1 is associated with the occurrence and development of human malignant tumors, making it a promising target for cancer immunotherapies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Kaizhen Wang, Ke Ye, Xiangyu Zhang, Tianyu Wang, Zhihao Qi, Youjun Wang, Sheng Jiang, Kuojun Zhang
Summary: Depleting NAD+ by blocking its biosynthesis has become an attractive anticancer strategy. Simultaneous blockade of NAD+ production from salvage and de novo synthesis pathways by targeting NAMPT and IDO1 could achieve more effective NAD+ reduction and, subsequently, more robust antitumor efficacy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Kuojun Zhang, Ke Ye, He Tang, Zhihao Qi, Tianyu Wang, Jie Mao, Xiangyu Zhang, Sheng Jiang
Summary: Janus kinases (JAKs) play important roles in cytokine signaling pathways, and small molecule JAK inhibitors have been developed to treat inflammatory and autoimmune diseases. Current research focuses on the discovery of isoform-selective JAK inhibitors, with TYK2 inhibition being a potential strategy to balance efficacy and safety. This article outlines the roles of TYK2 in diseases, reviews the advances of selective TYK2 inhibitors, and discusses future perspectives and challenges in TYK2 inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Tianyu Wang, Kaizhen Wang, Yu Zhang, Kuojun Zhang, Shi Cai, Sheng Jiang, Yibei Xiao, Xiangyu Zhang
Summary: Researchers have discovered a novel immune checkpoint called VISTA and developed bifunctional inhibitors to target it. These inhibitors effectively reverse VISTA-mediated immunosuppression and enhance the anti-tumor activity of immune cells. This discovery offers a new approach for cancer immunotherapy.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Shuai Zheng, Kuojun Zhang, Xiangyu Zhang, Yibei Xiao, Tianyu Wang, Sheng Jiang
Summary: Blocking PD-1/PD-L1 and CTLA-4 has limited therapeutic effect, so researchers are investigating more targets. VISTA has been identified as an appealing target for immunotherapy in various cancers. Several VISTA inhibitors are currently in clinical and preclinical trials.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Qi Miao, Wanheng Zhang, Kuojun Zhang, He Li, Jidong Zhu, Sheng Jiang
Summary: The optimized cyclic peptide JMPDP-027 interferes with the PD-1/PD-L1 protein-protein interaction and shows potent restoring ability towards T-cells, high resistance to enzymatic hydrolysis, no observable toxicity, and potent in vivo anticancer activity. This type of cyclic peptide antagonists may serve as novel drug candidates for cancer immunotherapy.