Article
Immunology
Yiwen Liang, Jingyi Shen, Qiu Lan, Kexin Zhang, Yan Xu, Maxwell Duah, Kailin Xu, Bin Pan
Summary: This research found that PD-1 expression on T cells increased in mice with chronic graft-versus-host disease (cGVHD). Intervention of the PD-1/PD-L1 pathway showed a significant impact on the occurrence of cGVHD and graft-versus-tumor effect.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
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
Immunology
Poyee Lau, Guanxiong Zhang, Shuang Zhao, Long Liang, Hailun Zhang, Guowei Zhou, Mien-Chie Hung, Xiang Chen, Hong Liu
Summary: This study reveals the important role of SPHK1 in tumor immunity and shows that its inhibition can suppress tumor growth and promote antitumor immunity. Additionally, SPHK1 and MTA3 are identified as biological markers for predicting the efficacy of anti-PD-1 mAb therapy in melanoma patients.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Oncology
Shengxiang Ren, Jifeng Feng, Shenglin Ma, HuaJun Chen, Zhiyong Ma, Cheng Huang, Li Zhang, Jianxing He, Changli Wang, Jianying Zhou, Pongwut Danchaivijtr, Chin-Chou Wang, Ihor Vynnychenko, Kai Wang, Francisco Orlandi, Virote Sriuranpong, Ben Li, Jun Ge, Thao Dang, Caicun Zhou
Summary: KEYNOTE-033 is a multicountry, open-label, phase 3 study that compared the efficacy of pembrolizumab and docetaxel in mainland China, in previously treated, PD-L1-positive, advanced NSCLC patients. The study showed that pembrolizumab improved overall survival compared to docetaxel in patients with PD-L1 TPS >= 1%. However, statistical significance was not reached in patients with PD-L1 TPS >= 50%. The performance of pembrolizumab in treating NSCLC is consistent with previous observations.
INTERNATIONAL JOURNAL OF CANCER
(2023)
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
Nishant Thakur, Kwang Yeol Paik, Gyoyeon Hwang, Yosep Chong
Summary: The study evaluated the expression and prognostic significance of immune checkpoint and EMT markers in periampullary cancers (PAC). It was found that high PD-L1 expression was significantly related to better overall survival (OS) and disease-free survival (DFS), while PD-L1 and PD-L2 were significantly related to EMT markers.
Article
Pharmacology & Pharmacy
Taisuke Kaiho, Hidemi Suzuki, Atsushi Hata, Hiroki Matsumoto, Kazuhisa Tanaka, Yuichi Sakairi, Shinichiro Motohashi, Ichiro Yoshino
Summary: Immune checkpoint molecules, such as PD-1 and PD-L1, have been shown to be important in lung cancer treatment. This study explored the role of these proteins in acute rejection in a mouse model of tracheal transplantation and found that PD-L1 Fc recombinant protein could decrease inflammatory cytokines and reduce the proportion of CD4+ T cells, suggesting a potential novel target for immunotherapy in lung transplantation.
FRONTIERS IN PHARMACOLOGY
(2023)
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.
Article
Oncology
Kiyohiro Ando, Kazuyuki Hamada, Midori Shida, Ryotaro Ohkuma, Yutaro Kubota, Atsushi Horiike, Hiroto Matsui, Tomoyuki Ishiguro, Yuya Hirasawa, Hirotsugu Ariizumi, Makoto Watanabe, Rie Onoue, Junji Tsurutani, Kiyoshi Yoshimura, Takuya Tsunoda, Shinichi Kobayashi, Satoshi Wada
Summary: The study investigated the prognostic impact of pretreatment PD-L1 expression levels in PBMC subsets in patients receiving anti-PD-1 blockade therapy. It was found that an increase in PD-L1 expression levels on CD14(+)monocytes was significantly associated with overall survival, suggesting a potential predictive role of PBMC in patients treated with immune checkpoint inhibitors.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Review
Immunology
Lin Zhang, Bo Hao, Zhihua Geng, Qing Geng
Summary: Toripalimab, a selective anti-PD-1 monoclonal antibody, has shown anti-tumor effects in melanoma, nasopharyngeal carcinoma, and urothelial carcinoma, and could be a valuable choice for future tumor treatment decision-making.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Alexander Hackel, Sebastian Vollmer, Kirsten Bruderek, Stephan Lang, Sven Brandau
Summary: This study evaluated the immunoregulatory properties of MSCs and their EVs, finding that primed MSCs and MSC-EVs had enhanced immunomodulatory effects, including increased induction of regulatory T cells and reduction of graft-versus-host disease. These effects were mediated through the PD-1 ligands.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Suxia Geng, Ruohao Xu, Xin Huang, Minming Li, Chengxin Deng, Peilong Lai, Yulian Wang, Ping Wu, Xiaomei Chen, Jianyu Weng, Xin Du
Summary: PD-1 expression significantly higher in high-risk MDS patients, and its increase during initial HMA treatment cycles may serve as an independent negative prognostic factor predicting AML transformation and survival. Monitoring PD-1 expression levels during HMA treatment cycles could help identify patients who may benefit from combined therapy with HMA and PD-1 inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, General & Internal
Mutiara Indah Sari, Syafruddin Ilyas
Summary: This systematic review evaluates the expression levels and concentrations of PD-1 and PD-L1 proteins in septic and other infectious patients.
Article
Biochemistry & Molecular Biology
Andrzej Kowalski, Katarzyna Malinowska, Jurek Olszewski, Hanna Zielinska-Blizniewska
Summary: The interaction of PD-1 and PD-L1 in laryngeal tumors allows cancer cells to escape from the immune system. Gene expression of PD-1 and PD-L1 was significantly higher in tumor tissue compared to unchanged mucosa, with higher expression levels associated with larger tumor sizes. These findings suggest potential for targeted immunotherapy with anti-PD1 and anti-PD-L1 monoclonal antibodies in treating laryngeal tumors.
Article
Immunology
Jorge Ibanez-Vega, Constanza Vilchez, Karin Jimenez, Carlos Guevara, Paula Burgos, Rodrigo Naves
Summary: The PD-1/PD-Ls pathway plays a key role in Multiple Sclerosis (MS) by inducing neuroprotective responses, restraining T cell activation, and neurodegeneration. Understanding the molecular and cellular mechanisms of PD-1/PD-Ls regulation and their involvement in the immunological synapse is crucial for the pathophysiology of MS.
JOURNAL OF AUTOIMMUNITY
(2021)
Article
Medicine, Research & Experimental
Adam L. Burrack, Zoe C. Schmiechen, Michael T. Patterson, Ebony A. Miller, Ellen J. Spartz, Meagan R. Rollins, Jackson F. Raynor, Jason S. Mitchell, Tsuneyasu Kaisho, Brian T. Fife, Ingunn M. Stromnes
Summary: We investigated the differential impact of myeloid subsets on immunity to pancreatic ductal adenocarcinoma (PDA). Our study demonstrates that tumor antigenicity shapes the composition and functionality of myeloid cells. The therapeutic effectiveness of adoptive T cell therapy or programmed cell death ligand 1 blockade relies on the presence of type 1 dendritic cells (cDC1), which support the survival and function of antitumor T cells. Our research highlights the essential role of cDC1s in sustaining effective antitumor T cells and reveals differential roles for cDC1s and monocytes/macrophages in guiding T cell fate and immunotherapy response.
Article
Multidisciplinary Sciences
Vijayakumar Velu, Kehmia Titanji, Hasan Ahmed, Ravi Dyavar Shetty, Lakshmi S. Chennareddi, Gordon J. Freeman, Rafi Ahmed, Rama Rao Amara
Summary: The study demonstrated that PD-1 blockade following ART interruption significantly enhances the function of anti-viral CD8 T cells and improves viral control. It suggests the potential synergistic effects of PD-1 blockade with other immunotherapies inducing functional CD8 T-cell responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Correction
Immunology
Christopher S. Garris, Sean P. Arlauckas, Rainer H. Kohler, Marcel P. Trefny, Seth Garren, Cecile Piot, Camilla Engblom, Christina Pfirschke, Marie Siwicki, Jeremy Gungabeesoon, Gordon J. Freeman, Sarah E. Warren, SuFey Ong, Erica Browning, Christopher G. Twitty, Robert H. Pierce, Mai H. Le, Alain P. Algazi, Adil I. Daud, Sara I. Pai, Alfred Zippelius, Ralph Weissleder, Mikael J. Pittet
Article
Multidisciplinary Sciences
Masao Hashimoto, Koichi Araki, Maria A. Cardenas, Peng Li, Rohit R. Jadhav, Haydn T. Kissick, William H. Hudson, Donald J. McGuire, Rebecca C. Obeng, Andreas Wieland, Judong Lee, Daniel T. McManus, James L. Ross, Se Jin Im, Junghwa Lee, Jian-Xin Lin, Bin Hu, Erin E. West, Christopher D. Scharer, Gordon J. Freeman, Arlene H. Sharpe, Suresh S. Ramalingam, Alex Pellerin, Volker Teichgraber, William J. Greenleaf, Christian Klein, Jorg J. Goronzy, Pablo Umana, Warren J. Leonard, Kendall A. Smith, Rafi Ahmed
Summary: The study showed that combination therapy with PD-1 blockade and IL-2 during chronic lymphocytic choriomeningitis virus infection significantly alters the differentiation program of CD8(+) T cells, resulting in the generation of highly functional effector CD8(+) T cells that mediate viral control, thus providing a new perspective for cancer treatment.
Article
Medicine, General & Internal
Elsa Brunet-Ratnasingham, Antigoni Morou, Mathieu Dube, Julia Niessl, Amy E. Baxter, Olivier Tastet, Nathalie Brassard, Gloria Ortega-Delgado, Roxanne Charlebois, Gordon J. Freeman, Cecile Tremblay, Jean-Pierre Routy, Daniel E. Kaufmann
Summary: This study examined the expression and function of immune checkpoints in CD4+ T cells of HIV-infected individuals and found that the expression of immune checkpoints is associated with infection status and effector profile. In addition, different subsets of CD4+ T cells show varying sensitivity to PD-1-mediated inhibition, suggesting heterogeneity in the restoration of cell function through immune checkpoint blockade.
Meeting Abstract
Hematology
Elisa Ten Hacken, Gabriela Brunsting Hoffmann, Kayla Cruz, Erin Michelle Parry, Elizabeth Witten, Donna S. Neuberg, Gordon J. Freeman, Catherine J. Wu
Article
Immunology
Magdiel Perez-Cruz, Bettina P. Iliopoulou, Katie Hsu, Hsin-Hsu Wu, Tom Erkers, Kavya Swaminathan, Sai-Wen Tang, Cameron S. Bader, Neeraja Kambham, Bryan Xie, Rosemarie H. Dekruyff, Gordon J. Freeman, Everett Meyer
Summary: The study suggests that RGMb may play a role in the pathogenesis of GvHD and IBD. Treatment with an anti-RGMb monoclonal antibody in mouse models prevented GvHD and IBD, while maintaining the graft-versus-tumor effect. The findings highlight the potential of targeting RGMb as a therapeutic strategy for these conditions.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Liya Ding, Qiwei Wang, Antons Martincuks, Michael J. Kearns, Tao Jiang, Ziying Lin, Xin Cheng, Changli Qian, Shaozhen Xie, Hye-Jung Kim, Inga-Maria Launonen, Anniina Faerkkilae, Thomas M. Roberts, Gordon J. Freeman, Joyce F. Liu, Panagiotis A. Konstantinopoulos, Ursula Matulonis, Hua Yu, Jean J. Zhao
Summary: This study reveals an adaptive immunosuppression mechanism that leads to resistance to PARP inhibition in BRCA1-mutant ovarian tumors. This resistance is mediated by an increased population of protumor tumor-associated macrophages (TAMs) and activation of the STAT3 signaling pathway. The use of STING agonists can reshape the immunosuppressive tumor microenvironment and overcome PARPi resistance in ovarian cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
John D. Klement, Priscilla S. Redd, Chunwan Lu, Alyssa D. Merting, Dakota B. Poschel, Dafeng Yang, Natasha M. Savage, Gang Zhou, David H. Munn, Padraic G. Fallon, Kebin Liu
Summary: This study found that tumor cell surface PD-L1 does not suppress cytotoxic T lymphocyte activity and has no effect on primary tumor growth. However, deletion of tumor cell surface PD-L1 decreases lung metastasis in a CTL-dependent manner. Depletion of myeloid cells or knocking out PD-1 in myeloid cells impairs PD-L1 promotion of tumor lung metastasis. Single-cell RNA sequencing revealed that PD-L1 engages myeloid cells PD-1 to activate SHP2 and repress the IFN-I-STAT1-CXCL9 pathway to impair CTL recruitment in lung metastasis.
Article
Multidisciplinary Sciences
Heng-Jia Liu, Heng Du, Damir Khabibullin, Mahsa Zarei, Kevin Wei, Gordon J. Freeman, David J. Kwiatkowski, Elizabeth P. Henske
Summary: This study reveals that B7-H3 expression is correlated with immunosuppressive phenotypes and worse clinical outcomes in human tumors with high mTORC1 activity. The authors show that mTORC1 upregulates B7-H3 expression by phosphorylating the transcription factor YY2. Inhibiting B7-H3 enhances T-cell activity and induces tumor cell expression of MHC-II, suppressing tumor growth with mTORC1 hyperactivity.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jing Liu, Xia Bu, Chen Chu, Xiaoming Dai, John M. Asara, Piotr Sicinski, Gordon J. Freeman, Wenyi Wei
Summary: The protein arginine methyltransferase PRMT1 suppresses the anti-tumor immune response by methylating cGAS and preventing its dimerization. Inhibition of PRMT1 activates the cGAS/STING-dependent DNA sensing signaling and increases the expression of interferon response genes, tumor-infiltrating lymphocytes, and tumoral PD-L1. Combination therapy of PRMT1 inhibitor with anti-PD-1 antibody enhances the anti-tumor therapeutic efficacy.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Satomi Ando, Charles M. Perkins, Yamato Sajiki, Chase Chastain, Rajesh M. Valanparambil, Andreas Wieland, William H. Hudson, Masao Hashimoto, Suresh S. Ramalingam, Gordon J. Freeman, Rafi Ahmed, Koichi Araki
Summary: T cell exhaustion is associated with dysfunction and expression of PD-1. mTOR inhibition during the expansion phase enhances T cell response, while inhibition after exhaustion progresses causes immunosuppression with decreased TIM3(+) cells and increased viral load. mTOR signaling is essential for differentiation of stem-like T cells into TIM3(+) cells.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Medicine, Research & Experimental
Justin A. Spanier, Vivian Fung, Christine M. Wardell, Mohannad H. Alkhatib, Yixin Chen, Linnea A. Swanson, Alexander J. Dwyer, Matthew E. Weno, Nubia Silva, Jason S. Mitchell, Paul C. Orban, Majid Mojibian, C. Bruce Verchere, Brian T. Fife, Megan K. Levings
Summary: Engineering Tregs with specific recognition for islet antigens using a chimeric antigen receptor (CAR) is a promising therapeutic approach for preventing autoimmune diabetes.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Meeting Abstract
Immunology
Melissa Tian Bu, Long Yuan, Alyssa Klee, Gordon J. Freeman
JOURNAL OF IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Jose Serrano, Maren R. Laughlin, Melena D. Bellin, Dhiraj Yadav, Vernon M. Chinchilli, Dana K. Andersen
Summary: Acute pancreatitis (AP) is inflammation of the pancreas and accounts for over 300,000 US hospital discharges annually. Recent studies have found that 30% to 40% of AP patients develop diabetes or impaired glucose tolerance within 3 to 4 years after a single episode of AP. To investigate the association between AP and type 1 diabetes, the National Institute of Diabetes and Digestive and Kidney Diseases funded the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC), which conducted a prospective observational study.