Article
Oncology
Ganji Purnachandra Nagaraju, Rama Rao Malla, Riyaz Basha, Ion G. Motofei
Summary: This review provides up-to-date information on the role of PD-1 and PD-L1 in the development of immune tolerance in pancreatic cancer and discusses current clinical trials and known outcomes. It also explores the involvement of PD-1/PD-L1 signaling in pancreatic cancer stem cells and metastasis. The review reviews the safety, tolerance, and efficacy of clinically important regimens of PD-1/PD-L1 blocking agents and targeted therapeutics.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Chemistry, Medicinal
Raphael Le Biannic, Romain Magnez, Frederique Klupsch, Natascha Leleu-Chavain, Bryan Thiroux, Morgane Tardy, Hassiba El Bouazzati, Xavier Dezitter, Nicolas Renault, Gerard Vergoten, Christian Bailly, Bruno Quesnel, Xavier Thuru, Regis Millet
Summary: Immuno-therapy using checkpoint inhibitor monoclonal antibodies against PD-1 and PD-L1 has shown improved survival in cancer patients. Researchers have synthesized a series of synthetic compounds with nanomolar activity against PD-L1 and characterized their properties using various biophysical techniques. Some small molecules demonstrated high affinity for human PD-L1, disrupting the PD-L1:PD-1 interaction effectively.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Yu Yuan, Abdalla Adam, Chen Zhao, Honglei Chen
Summary: Immune checkpoint blockade targeting PD-1/PD-L1 has shown promising therapeutic efficacy in various tumors, but resistance can hinder its effectiveness. This review examines the role of PD-L1 in therapy resistance, particularly through the PD-1/PD-L1 pathway, and highlights potential combination therapies to overcome this resistance.
Article
Oncology
Cinzia Vetrei, Margherita Passariello, Guendalina Froechlich, Rosa Rapuano Lembo, Nicola Zambrano, Claudia De Lorenzo
Summary: The study focuses on identifying potent and safe combinations of immunomodulatory monoclonal antibodies for cancer immunotherapy, using an in vitro system to predict efficacy and potential side effects early on. The research provides evidence of interactions between immune checkpoints in tumor cells and explores the functions of different immune checkpoints in cancer cells using clinically validated antibodies. Additionally, the study investigates novel combinations of immunomodulatory antibodies with greater anti-cancer activity and lower cardiotoxic effects.
Review
Chemistry, Multidisciplinary
Qian Wu, Li Jiang, Si-cheng Li, Qiao-jun He, Bo Yang, Ji Cao
Summary: PD-1/PD-L1 signaling pathway is a target for anticancer drugs, and the development of small molecule inhibitors provides a new avenue for tumor immunotherapy.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Pharmacology & Pharmacy
Katarzyna Magiera-Mularz, Katarzyna Kuska, Lukasz Skalniak, Przemyslaw Grudnik, Bogdan Musielak, Jacek Plewka, Justyna Kocik, Malgorzata Stec, Kazimierz Weglarczyk, Dominik Sala, Benedykt Wladyka, Maciej Siedlar, Tad A. Holak, Grzegorz Dubin
Summary: The study reports a macrocyclic peptide p101 capable of blocking the PD-L1/PD-1 immune checkpoint, showing that the interaction is primarily guided by hydrophobic forces. Experimental results demonstrate that p101 can effectively inhibit the interaction between PD-L1 and PD-1 in the cellular environment, releasing the immune response of human T cells.
ADVANCED THERAPEUTICS
(2021)
Article
Oncology
Debayan Mukherjee, Erminia Romano, Richard Walshaw, Leo A. H. Zeef, Antonia Banyard, Stephen J. Kitcatt, Eleanor J. Cheadle, Karoliina Tuomela, Swati Pendharkar, Aws Al-Deka, Beatrice Salerno, Sophie Raby, Ian G. Mills, Jamie Honeychurch, Tim M. Illidge
Summary: Despite advances in immune checkpoint inhibitors (ICI), many tumors still exhibit resistance and fail to respond to treatment. The combination of radiation therapy (RT) and ICI has not shown promising results in clinical trials. Therefore, novel approaches are needed to overcome this resistance and improve clinical outcomes.
Review
Immunology
Jianheng Luo, Ke Liu, Yong Wang, Hongge Li
Summary: This review briefly describes the immune response during I/R injury and how PD-L1 is involved in its regulation, focusing on findings from various I/R models. Despite the limited number of studies, PD-L1 has shown sufficient potential as a clinical therapeutic target.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Iris M. Hagemans, Peter J. Wierstra, Kas Steuten, Janneke D. M. Molkenboer-Kuenen, Duco van Dalen, Martin ter Beest, Johan M. S. van der Schoot, Olga Ilina, Martin Gotthardt, Carl G. Figdor, Ferenc A. Scheeren, Sandra Heskamp, Martijn Verdoes
Summary: A set of molecularly defined multimodal antibody-based PD-L1 imaging agents were synthesized and validated for multiscale monitoring of PD-L1 expression and localization. PEGylation of the Fab fragment improved its half-life and tumor uptake. PD-L1 in tumors was clearly visualized by SPECT/CT and whole body fluorescence imaging. The imaging agent's intratumoral localization could be determined with cellular resolution using fluorescent microscopy.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Editorial Material
Oncology
Michael R. Pitter, Weiping Zou
Summary: The article demonstrates that immune checkpoint blockade can enhance the response of tumor-specific T cells against tumor cells, effectively increasing tumor cell lysis, and provides scientific rationale for a new generation of cancer treatment targeting the PD-1/PD-L1 signaling pathway in the tumor microenvironment.
Article
Cell Biology
Jie Yu, Ai Zhuang, Xiang Gu, Yu Hua, Ludi Yang, Shengfang Ge, Jing Ruan, Peiwei Chai, Renbing Jia, Xianqun Fan
Summary: This study found that PD-L1 exists in the nucleus and is closely associated with poor outcomes in malignant tumors. Further experiments demonstrated that the presence of PD-L1 in the nucleus promotes cancer angiogenesis. Blocking the aberrant nuclear translocation of PD-L1 can offer a novel therapeutic strategy to inhibit tumor vascularization.
Article
Oncology
Fei Lu, Yanan Zhao, Yihua Pang, Min Ji, Yanping Sun, Hongchun Wang, Jie Zou, Yan Wang, Guosheng Li, Tao Sun, Jingxin Li, Daoxin Ma, Jingjing Ye, Chunyan Ji
Summary: The study revealed that NLRP3 inflammasome promotes immunosuppression in lymphoma by modulating PD-L1 and immune cells. Blockade of NLRP3 inflammasome can suppress lymphoma growth and improve anti-tumor immunity.
Article
Immunology
Besan H. Al-Saafeen, Ashraf Al-Sbiei, Ghada Bashir, Yassir A. Mohamed, Razan J. Masad, Maria J. Fernandez-Cabezudo, Basel K. al-Ramadi
Summary: This study demonstrates that a combination treatment using attenuated Salmonella and αPD-L1 antibody could improve the outcome of immunotherapy in colorectal cancer. The enhanced immune response is associated with reductions in tumor-associated granulocytic cells, upregulation in MHC class II expression by intratumoral monocytes, and increased tumor infiltration by effector T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Anudari Letian, Eyoel Yemanaberhan Lemma, Paola Cavaliere, Noah Dephoure, Nasser K. Altorki, Timothy E. McGraw
Summary: PD-L1, a transmembrane ligand for immune checkpoint receptor PD1, has been successfully targeted to activate anti-tumor immune response in various solid tumors, including NSCLC. However, only a small percentage of patients respond to the treatment. This study reveals the growth factor control of PD-L1 recycling as a mechanism for regulating PD-L1 density on the plasma membrane, and identifies novel PD-L1 biology specific to mutant EGFR cells. The study also shows that anti-PD-L1 treatment affects mutant EGFR cells differently, leading to reduced cell migration, increased EGFR stability, and increased extracellular vesicle biogenesis.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Biochemistry & Molecular Biology
Fabio Morandi, Irma Airoldi
Summary: HLA-G is an HLA-class Ib molecule involved in tolerance establishment during pregnancy. The expression of HLA-G is restricted in adults but can be observed in tumors, where it contributes to immune escape and tumor progression. It interacts with other immune checkpoint molecules like PD-1, CTLA-4, TIM-3, IDO, and TIGIT. Clinical trials using monoclonal antibodies against HLA-G and other immune checkpoints have shown promising results in cancer patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Patrick P. C. Boor, Kostandinos Sideras, Katharina Biermann, M. Hosein Aziz, Iris J. M. Levink, Shanta Mancham, Nicole S. Erler, Xudong Tang, Casper H. van Eijck, Marco J. Bruno, Dave Sprengers, Xingxing Zang, Jaap Kwekkeboom
BRITISH JOURNAL OF CANCER
(2020)
Article
Virology
Robert H. Bortz, Anthony C. Wong, Michael G. Grodus, Hannah S. Recht, Marc C. Pulanco, Gorka Lasso, Simon J. Anthony, Eva Mittler, Rohit K. Jangra, Kartik Chandran
JOURNAL OF VIROLOGY
(2020)
Article
Oncology
Ziqiang Yuan, Juliet C. Gardiner, Elaine C. Maggi, Shuyu Huang, Asha Adem, Svetlana Bagdasarov, Guiying Li, Sylvia Lee, Daniel Slegowski, Alyssa Exarchakis, James R. Howe, Edmund C. Lattime, Xingxing Zang, Steven K. Libutti
Summary: The study found that HHLA2 and B7x are highly expressed in GINETs and PNETs, and correlate with malignancy and spread. The overexpression of HIF-1 alpha is associated with the upregulation of B7x, and Men1/B7x double knockout mice show increased T-cell infiltration. Targeting B7x may offer a promising strategy for immunotherapy in patients with NETs.
ENDOCRINE-RELATED CANCER
(2021)
Article
Oncology
Phillip M. Galbo, Xingxing Zang, Deyou Zheng
Summary: This study conducted a comprehensive analysis of CAFs from multiple cancer types, identified shared molecular characteristics in CAF subtypes, and revealed the association of different CAF subtypes with clinical outcomes and immunotherapy resistance.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Wei Zhang, Ana Acuna-Villaorduna, Kevin Kuan, Sorab Gupta, Shaomin Hu, Kim Ohaegbulam, Joseph Albanese, Meghan Kaumaya, Rachel Levy, Richard R. Hwang, Xingxing Zang, Juan Lin, Qiang Liu, Radhashree Maitra, Sanjay Goel
Summary: Low expression of both PD-L1 and B7-H3 in colorectal cancer is associated with better survival outcomes, without significant variation among different racial groups in terms of relevant protein markers for CRC.
CLINICAL COLORECTAL CANCER
(2021)
Article
Oncology
Qianghua Zhou, Kaiwen Li, Yiming Lai, Kai Yao, Qiong Wang, Xiangyu Zhan, Shirong Peng, Wenli Cai, Wei Yao, Xingxing Zang, Kewei Xu, Jian Huang, Hai Huang
Summary: Both B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment in PCa. The B7 score, combined with CD8(+) TILs, can be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Yao Wei, Xiaoxin Ren, Phillip M. Galbo, Scott Moerdler, Hao Wang, R. Alejandro Sica, Bijan Etemad-Gilbertson, Lei Shi, Liqiang Zhu, Xudong Tang, Qi Lin, Mou Peng, Fangxia Guan, Deyou Zheng, Jordan M. Chinai, Xingxing Zang
Summary: HHLA2 is a promising target for cancer immunotherapy due to its coinhibitory function and overexpression in human cancers. The KIR3DL3-HHLA2 pathway may be a potential immunotherapeutic target for cancer.
SCIENCE IMMUNOLOGY
(2021)
Article
Hematology
Ilseyar Akhmetzyanova, Tonya Aaron, Phillip Galbo, Anastasia Tikhonova, Igor Dolgalev, Masato Tanaka, Iannis Aifantis, Deyou Zheng, Xingxing Zang, David Fooksman
Summary: The dissemination and progression of multiple myeloma is associated with an increased inflammatory signature in bone marrow MPs, with CD169(+) MPs playing a critical role in the early spread of myeloma.
Article
Multidisciplinary Sciences
Peter John, Marc C. Pulanco, Phillip M. Galbo, Yao Wei, Kim C. Ohaegbulam, Deyou Zheng, Xingxing Zang
Summary: B7x, an immune checkpoint molecule, promotes the conversion of CD4+ T cells into regulatory T cells within the tumor microenvironment. It induces transcriptomic changes in regulatory T cells, altering their phenotype to an activated and suppressive state. B7x-mediated regulation reduces the efficacy of anti-CTLA-4 treatment, but combination therapy with anti-B7x and anti-CTLA-4 overcomes this resistance and shows synergistic therapeutic efficacy.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Elodie Picarda, Phillip M. Galbo, Haihong Zong, Meenu Rohini Rajan, Ville Wallenius, Deyou Zheng, Emma Borgeson, Rajat Singh, Jeffrey Pessin, Xingxing Zang
Summary: The immune checkpoint B7-H3 has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. This study reveals that B7-H3 is highly expressed in adipose tissue, particularly in adipocyte progenitor cells, and it regulates the glycolytic and mitochondrial activity of these cells. Loss of B7-H3 leads to impaired oxidative metabolism and increased lipid accumulation in derived adipocytes. Knockout of B7-H3 in mice results in spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation.
Review
Immunology
Marc C. Pulanco, Anne T. Madsen, Ankit Tanwar, Devin T. Corrigan, Xingxing Zang
Summary: The B7/CD28 families of immune checkpoints play important roles in regulating immune cells and are closely related to various diseases. Recent studies have discovered new pathways and therapeutics for cancer therapy in this field. This review covers the newly discovered KIR3DL3/TMIGD2/HHLA2 pathways, metabolic regulation by PD-1/PD-L1 and B7-H3, the glycobiology of PD-1/PD-L1, B7x, and B7-H3, as well as the interaction between PD-L1 and B7-1. The article also discusses the resistance mechanisms to current immunotherapies targeting PD-1/PD-L1 and CTLA-4 in clinical settings, and reviews new immunotherapies targeting B7-H3, B7x, PD-1/PD-L1, and CTLA-4 in ongoing clinical trials.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Xiaoxin Ren, Yixian Li, Christopher Nishimura, Xingxing Zang
Summary: Somatic activating mutations in EGFR are common in various cancers. Targeted therapies against EGFR have shown clinical efficacy, but acquired resistance is a challenge. PD-1/PD-L1 immune checkpoint inhibitors are effective in some cancers, but limited in EGFR mutated cancers. Up-regulation of new B7/CD28 family members related to EGFR signaling may contribute to immunosuppressive tumor microenvironment and resistance to EGFR-targeted therapies. Understanding these interactions could inform combination therapeutic strategies.
Article
Oncology
Scott Moerdler, Michelle Ewart, Debra L. Friedman, Kara Kelly, Qinglin Pei, Mou Peng, XingXing Zang, Peter D. Cole
Summary: In pediatric Hodgkin lymphoma, LAG-3 expression is found to be positively correlated with PD-L1 expression, serving as an innovative immune checkpoint target with unclear association to patient outcomes.
LEUKEMIA & LYMPHOMA
(2021)