Review
Medicine, Research & Experimental
Sajad Najafi, Jamal Majidpoor, Keywan Mortezaee
Summary: Immune checkpoint inhibitors have revolutionized cancer treatment, and the composition of gut microbiota may serve as a potential biomarker for predicting immunotherapy response. Fecal microbiota transplantation and certain bacterial components may improve clinical outcomes and overcome resistance to immunotherapy.
Review
Immunology
Shimeng Zhou, Jinfeng Zhu, Jingwei Xu, Bingzi Gu, Qiao Zhao, Congzhou Luo, Zhoufeng Gao, Y. Eugene Chin, Xiaju Cheng
Summary: The PD-L1/PD-1 signaling pathway is considered one of the main mechanisms of tumor escape from immune surveillance. PD-L1 is highly expressed on tumor cells and binds to the PD-1 receptor on activated T cells, inhibiting their anti-tumor activity. Recent research has focused on post-translational modifications of PD-L1/PD-1, such as glycosylation, ubiquitination, phosphorylation, and acetylation, and their potential role in regulating the signaling pathway and anti-tumor function of T cells.
Article
Oncology
Francesco Spagnolo, Andrea Boutros, Federica Cecchi, Elena Croce, Enrica Teresa Tanda, Paola Queirolo
Summary: Treatment beyond progression with anti-PD-1/PD-L1 therapy in patients with advanced solid tumors may lead to unconventional responses, with a proportion of patients achieving clinical benefit. It is crucial for future trials investigating immunotherapy to provide more comprehensive information on immune-related clinical activity to guide treatment decisions for advanced cancer patients.
Review
Biochemistry & Molecular Biology
Xinfang Yu, Wei Li, Ken H. Young, Yong Li
Summary: PD-L1 is a classic immune checkpoint molecule with its expression regulated by posttranslational modifications (PTMs) that play vital roles in controlling PD-L1 expression, cellular trafficking, and antitumor immune response.
Review
Oncology
F. Martorana, I. Colombo, G. Treglia, S. Gillessen, A. Stathis
Summary: Phase II trials evaluating the combinations of PD-1/PD-L1 inhibitors with other anti-cancer therapies are diverse, with PD-1 inhibitors being the most frequently studied. Only a minority of indications have received regulatory approval from authorities.
CANCER TREATMENT REVIEWS
(2021)
Article
Oncology
Lucile Vanhersecke, Maxime Brunet, Jean-Philippe Guegan, Christophe Rey, Antoine Bougouin, Sophie Cousin, Sylvestre Le Moulec, Benjamin Besse, Yohann Loriot, Mathieu Larroquette, Isabelle Soubeyran, Maud Toulmonde, Guilhem Roubaud, Simon Pernot, Mathilde Cabart, Francois Chomy, Corentin Lefevre, Kevin Bourcier, Michele Kind, Ilenia Giglioli, Catherine Sautes-Fridman, Valerie Velasco, Felicie Courgeon, Ezoglin Oflazoglu, Ariel Savina, Aurelien Marabelle, Jean-Charles Soria, Carine Bellera, Casimir Sofeu, Alban Bessede, Wolf H. Fridman, Francois Le Loarer, Antoine Italiano
Summary: The presence of mature tertiary lymphoid structures is associated with improved response to immunotherapy in cancer patients, predicting objective response rates, progression-free survival, and overall survival. These findings support the potential use of TLS detection to select patients who are more likely to benefit from immune checkpoint blockade.
Article
Chemistry, Medicinal
Chengliang Sun, Mingxiao Yin, Yao Cheng, Zean Kuang, Xiaojia Liu, Gefei Wang, Xiao Wang, Kai Yuan, Wenjian Min, Jingwen Dong, Yi Hou, Lingrong Hu, Guoyu Zhang, Wenli Pei, Liping Wang, Yanze Sun, Xinmiao Yu, Yibei Xiao, Hongbin Deng, Peng Yang
Summary: S4-1 is an innovative small-molecule inhibitor of PD-L1 that effectively alters the PD-L1/PD-1 interaction, enhances cytotoxicity of immune cells towards tumor cells, and shows significant tumor growth inhibition in vivo. It also activates T-cells and reverses the inhibitory tumor microenvironment.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Canete-Portillo, Maria Paola Bonasoni, Alessandra Soriano, Stefano Ascani, Maurizio Zizzo, Carolina Castro Ruiz, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Daniel M. Berney, Jatin Gandhi, Davide Nicoli, Enrico Farnetti, Giacomo Santandrea, Martina Bonacini
Summary: Epigenetic alterations impact the expression of PD-L1 in prostate cancer, with DNA methylation and miRNAs being key factors. Histone modifiers and epigenetic drugs can reverse these alterations. miRNAs can regulate PD-L1 post-transcriptionally, offering potential clinical applications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Clemens Zwergel, Rossella Fioravanti, Antonello Mai
Summary: Programmed death-ligand 1 (PD-L1) is an immune checkpoint protein that, when overexpressed, induces an inhibitory signal causing T cell exhaustion and immune escape in tumors. Immunotherapy targeting the PD-L1 pathway has successfully treated various cancers. Recent advances in understanding the complex biology of PD-L1 have led to the development of small-molecule inhibitors. This review highlights the most promising recent advances in understanding the regulation mechanisms of PD-L1 and the use of small-molecule modulators in combination therapy with other epigenetic chemotherapeutic agents.
DRUG DISCOVERY TODAY
(2023)
Review
Biochemistry & Molecular Biology
Liping Pei, Yang Liu, Lin Liu, Shuochen Gao, Xueyan Gao, Yudi Feng, Zhenqiang Sun, Yan Zhang, Chengzeng Wang
Summary: Breakthroughs in tumor immunotherapy have been made in recent years, but its effectiveness in solid cancer, especially anti-PD-1/PD-L1 immune checkpoint inhibitors, is limited to a small percentage of patients. Improving the efficiency of cancer immunotherapy is an urgent problem. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) have attracted attention due to their interaction with cancer cells and immune cells, affecting the immune response process. The heterogeneity of CAFs provides new strategies for combination immunotherapy targets and predicting immune efficacy.
Article
Oncology
Giulia Cossu, Stefano La Rosa, Jean Philippe Brouland, Nelly Pitteloud, Ethan Harel, Federico Santoni, Maxime Brunner, Roy Thomas Daniel, Mahmoud Messerer
Summary: The expression of PD-L1 is associated with proliferative grades of Trouillas' classification and specific subtypes of PitNET expressing growth hormone.
Article
Multidisciplinary Sciences
Changsheng Huang, Shengxiang Ren, Yaqi Chen, Anyi Liu, Qi Wu, Tao Jiang, Panjing Lv, Da Song, Fuqing Hu, Jingqing Lan, Li Sun, Xue Zheng, Xuelai Luo, Qian Chu, Keyi Jia, Yan Li, Jun Wang, Caicun Zou, Junbo Hu, Guihua Wang
Summary: This research discovered that PD-L1 K162 was methylated by SETD7 and demethylated by LSD2. Additionally, PD-L1 K162 methylation controlled the PD1/PD-L1 interaction and significantly enhanced the suppression of T cell activity in controlling cancer immune surveillance. The study demonstrated that PD-L1 hypermethylation was the key mechanism for anti-PD-L1 therapy resistance, identified PD-L1 K162 methylation as a negative predictive marker for anti-PD-1 treatment in patients with non-small cell lung cancer, and showed that the PD-L1 K162 methylation:PD-L1 ratio was a more accurate biomarker for predicting anti-PD-(L)1 therapy sensitivity.
Article
Medicine, General & Internal
Dan Liu, Jun Zhou, Yongsheng Wang, Mingjun Li, Haiping Jiang, Yunpeng Liu, Xianli Yin, Minghua Ge, Xiaojun Xiang, Jieer Ying, Jian Huang, Yan-qiao Zhang, Ying Cheng, Zhigang Huang, Xianglin Yuan, Weiqing Han, Dong Yan, Xinshuai Wang, Pan Liu, Linna Wang, Xiaojing Zhang, Suxia Luo, Tianshu Liu, Lin Shen
Summary: SHR-1701, a novel bifunctional fusion protein targeting PD-1/PD-L1 and TGF-beta pathways, showed promising antitumor activity and an acceptable safety profile, especially in gastric cancer patients.
Review
Medicine, General & Internal
X. Sun, T. Zhang, M. Li, L. Yin, J. Xue
Summary: This review discusses the expression of PD-1/PD-L1 on B cells and their immunosuppressive role in solid tumors, aiming to explore the potential for diagnostic tools and new therapies involving this unique group of cells.
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Philipp Knopf, Dimitri Stowbur, Sabrina H. L. Hoffmann, Natalie Hermann, Andreas Maurer, Valentina Bucher, Marilena Poxleitner, Bredi Tako, Dominik Sonanini, Balaji Krishnamachary, Sanhita Sinharay, Birgit Fehrenbacher, Irene Gonzalez-Menendez, Felix Reckmann, David Bomze, Lukas Flatz, Daniela Kramer, Martin Schaller, Stephan Forchhammer, Zaver M. Bhujwalla, Leticia Quintanilla-Martinez, Klaus Schulze-Osthoff, Mark D. Pagel, Marieke F. Fransen, Martin Roecken, Andre F. Martins, Bernd J. Pichler, Kamran Ghoreschi, Manfred Kneilling
Summary: This study reveals that acidosis can increase the expression of PD-L1 on cancer cells, promoting tumor immune escape. Preclinical models confirm this finding and show that neutralizing the acidic tumor environment can suppress PD-L1 expression and promote immune cell infiltration, reducing tumor growth.