Letter
Biochemistry & Molecular Biology
Ismael Rodriguez, Justyna Kocik-Krol, Lukasz Skalniak, Bogdan Musielak, Aneta Wisniewska, Agnieszka Ciesiolkiewicz, Lukasz Berlicki, Jacek Plewka, Przemyslaw Grudnik, Malgorzata Stec, Maciej Siedlar, Tad A. Holak, Katarzyna Magiera-Mularz
Summary: Recent advances in immuno-oncology have brought new treatment options for cancer. Macrocyclic peptides with strong binding strengths to PD-L1 have been developed. The pAC65 peptide, a non-antibody-based PD-1/PD-L1 inhibitor, shows potency similar to FDA-approved mAbs and may have potential in immunotherapy for cancer and other immune-related disorders.
Article
Medicine, General & Internal
Suleyman Ozdemir, Ozlem Ton, Fevziye Kabukcuoglu
Summary: This study aimed to investigate the expression of PD-L1 in classical Hodgkin lymphoma (CHL) patients and compare it with clinical parameters and prognosis. The results showed a high prevalence of PD-L1 positivity in CHL patients, but no significant difference was found with EBV expression, clinical parameters, and prognosis. Therefore, PD-L1 may be a potential target for emerging immunotherapies for CHL.
TURKISH JOURNAL OF MEDICAL SCIENCES
(2022)
Article
Oncology
Yu Feng, Liguo Liu, Jing Li, Jia Huang, Jenny H. Xie, Laurence Menard, Yanfen Shi, Xiaohong Zhao, Shan Xie, Wenjuan Zang, Haidong Tan, Zhiying Yang, Ling Ni
Summary: This study reveals the presence of NR4A2 B cells in the tumor microenvironment of hepatocellular carcinoma (HCC), which may play a negative role in antitumor immunity and are significantly correlated with PD-L1 expression. Therefore, B cells may serve as a promising immunotherapeutic target for HCC treatment.
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
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
Oncology
Yutao Li, Amit Sharma, Maurits Bloemendal, Roland Schmidt-Wolf, Miroslaw Kornek, Ingo Schmidt-Wolf
Summary: CIK cells have cytotoxic effects on B-NHL cells, and a combination therapy of PD-1 inhibitors with CIK cells may offer a potential treatment option for this type of lymphoma. Further in vivo experiments are needed to determine the extent of enhancement of antitumor activity in B-NHL by PD-1 inhibitors.
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
Medicine, General & Internal
Kazuhiko Hashimoto, Shunji Nishimura, Naoki Sakata, Masami Inoue, Akihisa Sawada, Masao Akagi
Summary: Recent data suggest that PD-1 and PD-L1 are involved in the pathogenesis of Langerhans cell histiocytoma (LCH), with high expression rates observed in musculoskeletal LCH cases. This study evaluated PD-1/PD-L1 expression in 6 patients with musculoskeletal LCH, finding potential roles for these immune checkpoint molecules in the disease microenvironment.
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.
Review
Pharmacology & Pharmacy
Ze Xiang, Jiayuan Li, Zhengyu Zhang, Chao Cen, Wei Chen, Bin Jiang, Yiling Meng, Ying Wang, Bjoern Berglund, Guanghua Zhai, Jian Wu
Summary: Immunotherapy with immune checkpoint inhibitor (ICI) drugs is a hot topic in cancer treatment. Our study used Bayesian model to comprehensively evaluate the safety and efficacy of ICI drugs. Different ICI drug therapies may have different risks in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Treatment with cemiplimab was found to be the best choice in terms of PFS and OS. Our study provides new insights and strategies for the clinical practice of ICI drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Naoya Maekawa, Satoru Konnai, Yumie Asano, Takumi Otsuka, Eri Aoki, Hiroto Takeuchi, Yukinari Kato, Mika K. Kaneko, Shinji Yamada, Yumiko Kagawa, Maki Nishimura, Satoshi Takagi, Tatsuya Deguchi, Hiroshi Ohta, Takayuki Nakagawa, Yasuhiko Suzuki, Tomohiro Okagawa, Shiro Murata, Kazuhiko Ohashi
Summary: This study investigated the potential use of anti-PD-1/PD-L1 therapy in feline tumors. The researchers determined the coding sequence of feline PD-L1 and PD-L2, and confirmed the binding between PD-1 and PD-L1/PD-L2. They also discovered the expression of PD-L1 in various feline tumor tissues. The results suggest that further investigation of the PD-1/PD-L1 pathway could be a promising therapeutic target for feline tumors.
Meeting Abstract
Oncology
Erica S. Tsang, James T. Topham, Joanna Karasinska, Steve Kalloger, Veronika Csizmok, Laura Williamson, Hui-Li Wong, Grainne M. O'Kane, Jonathan M. Loree, Faiyaz Notta, Oliver F. Bathe, Patricia A. Tang, Rachel Anne Goodwin, Jennifer J. Knox, Steven Gallinger, Janessa J. Laskin, Marco A. Marra, Steven J. M. Jones, David F. Schaeffer, Daniel John Renouf
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Stephen D. Lee, Jungeun Song, Veronique G. LeBlanc, Marco A. Marra
Summary: It has been found that CIC's transcriptional repressor function is related to neurodevelopment and IDH-mutant glioma progression. Comparative analysis of transcriptomic and epigenomic profiles revealed dysregulation of neurodevelopmental genes associated with CIC loss, as well as the discovery of new direct CIC target genes linked to neurodevelopment and glioma pathogenesis.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemical Research Methods
Simon Haile, Aidan M. Nikiforuk, Pawan K. Pandoh, David D. W. Twa, Duane E. Smailus, Jason Nguyen, Stephen Pleasance, Angus Wong, Yongjun Zhao, Diane Eisler, Michelle Moksa, Qi Cao, Marcus Wong, Edmund Su, Martin Krzywinski, Jessica Nelson, Andrew J. Mungall, Frankie Tsang, Leah M. Prentice, Agatha Jassem, Amee R. Manges, Steven J. M. Jones, Robin J. Coope, Natalie Prystajecky, Marco A. Marra, Mel Krajden, Martin Hirst
Summary: The COVID-19 pandemic has shown the importance of generic reagents and flexible systems in diagnostic testing. Magnetic bead-based nucleic acid extraction protocols using 96-well plates on open liquid handlers have been optimized to reduce cross-well contamination and maintain sensitivity.
JOURNAL OF VIROLOGICAL METHODS
(2022)
Article
Multidisciplinary Sciences
Caralyn Reisle, Laura M. Williamson, Erin Pleasance, Anna Davies, Brayden Pellegrini, Dustin W. Bleile, Karen L. Mungall, Eric Chuah, Martin R. Jones, Yussanne Ma, Eleanor Lewis, Isaac Beckie, David Pham, Raphael Matiello Pletz, Amir Muhammadzadeh, Brandon M. Pierce, Jacky Li, Ross Stevenson, Hansen Wong, Lance Bailey, Abbey Reisle, Matthew Douglas, Melika Bonakdar, Jessica M. T. Nelson, Cameron J. Grisdale, Martin Krzywinski, Ana Fisic, Teresa Mitchell, Daniel J. Renouf, Stephen Yip, Janessa Laskin, Marco A. Marra, Steven J. M. Jones
Summary: Manual interpretation of variants remains a limitation in precision oncology. To address this, the authors introduce an open-source platform called PORI to interpret and report somatic variants in cancer. PORI integrates reporting and graph knowledge base tools, and supports manual curation, suitable for comprehensive genomic datasets.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Dollina D. Dodani, Matthew H. Nguyen, Ryan D. Morin, Marco A. Marra, Richard D. Corbett
Summary: Formalin fixation of paraffin-embedded tissue samples is a commonly used method for tissue preservation, but it causes molecular damage to nucleic acids, which affects their use in genome sequence analysis. This study optimized a sensitive and precise single nucleotide variant calling approach for FFPE samples using whole-genome sequencing data. Combinatorial and statistical techniques were used to reduce false-positive variants, and a novel variant classification method was introduced.
FRONTIERS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Elodie Bal, Rahul Kumar, Mohammad Hadigol, Antony B. Holmes, Laura K. Hilton, Jui Wan Loh, Kostiantyn Dreval, Jasper C. H. Wong, Sofija Vlasevska, Clarissa Corinaldesi, Rajesh Kumar Soni, Katia Basso, Ryan D. Morin, Hossein Khiabanian, Laura Pasqualucci, Riccardo Dalla-Favera
Summary: This study found that super-enhancers in the non-coding genome of DLBCL patients are highly mutated and linked to B cell developmental regulators and oncogenes. The mutations in these super-enhancers prevent the binding of transcriptional repressors and downregulation of target genes, indicating an oncogenic dependency. This research expands the involvement of known oncogenes in DLBCL pathogenesis and identifies new deregulated gene targets of therapeutic relevance.
Article
Plant Sciences
Kristina K. Gagalova, Rene L. Warren, Lauren Coombe, Johnathan Wong, Ka Ming Nip, Macaire Man Saint Yuen, Justin G. A. Whitehill, Jose M. Celedon, Carol Ritland, Greg A. Taylor, Dean Cheng, Patrick Plettner, S. Austin Hammond, Hamid Mohamadi, Yongjun Zhao, Richard A. Moore, Andrew J. Mungall, Brian Boyle, Jerome Laroche, Joan Cottrell, John J. Mackay, Manuel Lamothe, Sebastien Gerardi, Nathalie Isabel, Nathalie Pavy, Steven J. M. Jones, Joerg Bohlmann, Jean Bousquet, Inanc Birol
Summary: This study compares the genomes of four different North American spruces and finds that their genome structures are similar, but rapidly evolving genomes indicate signs of divergent evolution, related to environmental adaptation and stress response.
Article
Oncology
Min Xia, Liron David, Matt Teater, Johana Gutierrez, Xiang Wang, Cem Meydan, Andrew Lytle, Graham W. Slack, David W. Scott, Ryan D. Morin, Ozlem Onder, Kojo S. J. Elenitoba-Johnson, Nahuel Zamponi, Leandro Cerchietti, Tianbao Lu, Ulrike Philippar, Lorena Fontan, Hao Wu, Ari M. Melnick
Summary: BCL10 mutations in ABC-DLBCL can be classified into two distinct biochemical classes, with both conferring resistance to BTK inhibitors and BCL10 truncations conferring hypersensitivity to MALT1 inhibitors, providing a roadmap for precision therapies in ABC-DLBCLs.
Letter
Hematology
Christopher K. Rushton, Kostiantyn Dreval, Ryan D. Morin
Article
Hematology
Kostiantyn Dreval, Paul C. Boutros, Ryan D. Morin
Summary: Exome and genome sequencing have identified recurring mutations in hundreds of genes and regions in hematologic neoplasms. However, quality differences between data sets can affect secondary analyses. It is important to establish a minimum reporting standard to improve transparency in genomic research.
Article
Multidisciplinary Sciences
James T. Topham, Erica S. Tsang, Joanna M. Karasinska, Andrew Metcalfe, Hassan Ali, Steve E. Kalloger, Veronika Csizmok, Laura M. Williamson, Emma Titmuss, Karina Nielsen, Gian Luca Negri, Sandra E. Spencer Miko, Gun Ho Jang, Robert E. Denroche, Hui-li Wong, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Jonathan M. Loree, Faiyaz Notta, Julie M. Wilson, Oliver F. Bathe, Patricia A. Tang, Rachel Goodwin, Gregg B. Morin, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J. M. Jones, David F. Schaeffer, Daniel J. Renouf
Summary: KRAS wildtype mPDAC may represent a distinct molecular entity with similarities to cholangiocarcinoma. There may be therapeutic options beyond standard-of-care cytotoxic chemotherapy for this subgroup of mPDAC patients.
NATURE COMMUNICATIONS
(2022)
Meeting Abstract
Hematology
Brett Collinge, Susana Ben-Neriah, Laura K. Hilton, Waleed Alduaij, Tracy Tucker, Graham W. Slack, Pedro Farinha, Jeffrey W. Craig, Merrill Boyle, Barbara Meissner, Kelly Mekwunye, Alina S. Gerrie, Laurie H. Sehn, Kerry J. Savage, Ryan D. Morin, Andrew J. Mungall, Christian Steidl, David W. Scott
Correction
Multidisciplinary Sciences
Liam D. Hendrikse, Parthiv Haldipur, Olivier Saulnier, Jake Millman, Alexandria H. Sjoboen, Anders W. Erickson, Winnie Ong, Victor Gordon, Ludivine Coudiere-Morrison, Audrey L. Mercier, Mohammad Shokouhian, Raul A. Suarez, Michelle Ly, Stephanie Borlase, David S. Scott, Maria C. Vladoiu, Hamza Farooq, Olga Sirbu, Takuma Nakashima, Shohei Nambu, Yusuke Funakoshi, Alec Bahcheli, J. Javier Diaz-Mejia, Joseph Golser, Kathleen Bach, Tram Phuong-Bao, Patryk Skowron, Evan Y. Wang, Sachin A. Kumar, Polina Balin, Abhirami Visvanathan, John J. Y. Lee, Ramy Ayoub, Xin Chen, Xiaodi Chen, Karen L. Mungall, Betty Luu, Pierre Berube, Yu C. Wang, Stefan M. Pfister, Seung-Ki Kim, Olivier Delattre, Franck Bourdeaut, Francois Doz, Julien Masliah-Planchon, Wieslawa A. Grajkowska, James Loukides, Peter Dirks, Michelle Fevre-Montange, Anne Jouvet, Pim J. French, Johan M. Kros, Karel Zitterbart, Swneke D. Bailey, Charles G. Eberhart, Amulya A. N. Rao, Caterina Giannini, James M. Olson, Miklos Garami, Peter Hauser, Joanna J. Phillips, Young S. Ra, Carmen de Torres, Jaume Mora, Kay K. W. Li, Ho-Keung Ng, Wai S. Poon, Ian F. Pollack, Enrique Lopez-Aguilar, G. Yancey Gillespie, Timothy E. Van Meter, Tomoko Shofuda, Rajeev Vibhakar, Reid C. Thompson, Michael K. Cooper, Joshua B. Rubin, Toshihiro Kumabe, Shin Jung, Boleslaw Lach, Achille Iolascon, Veronica Ferrucci, Pasqualino de Antonellis, Massimo Zollo, Giuseppe Cinalli, Shenandoah Robinson, Duncan S. Stearns, Erwin G. Van Meir, Paola Porrati, Gaetano Finocchiaro, Maura Massimino, Carlos G. Carlotti, Claudia C. Faria, Martine F. Roussel, Frederick Boop, Jennifer A. Chan, Kimberly A. Aldinger, Ferechte Razavi, Evelina Silvestri, Roger E. McLendon, Eric M. Thompson, Marc Ansari, Maria L. Garre, Fernando Chico, Pilar Eguia, Mario Perezpena, A. Sorana Morrissy, Florence M. G. Cavalli, Xiaochong Wu, Craig Daniels, Jeremy N. Rich, Steven J. M. Jones, Richard A. Moore, Marco A. Marra, Xi Huang, Juri Reimand, Poul H. Sorensen, Robert J. Wechsler-Reya, William A. Weiss, Trevor J. Pugh, Livia Garzia, Claudia L. Kleinman, Lincoln D. Stein, Nada Jabado, David Malkin, Olivier Ayrault, Jeffrey A. Golden, David W. Ellison, Brad Doble, Vijay Ramaswamy, Tamra E. Werbowetski-Ogilvie, Hiromichi Suzuki, Kathleen J. Millen, Michael D. Taylor
Article
Biochemistry & Molecular Biology
E. Titmuss, K. Milne, M. R. Jones, T. Ng, J. T. Topham, S. D. Brown, D. F. Schaeffer, S. Kalloger, D. Wilson, R. D. Corbett, L. M. Williamson, K. Mungall, A. J. Mungall, R. A. Holt, B. H. Nelson, S. J. M. Jones, J. Laskin, H. J. Lim, M. A. Marra
Summary: The POG program at BC Cancer identified specific alterations in colorectal cancer using whole genome and transcriptome analysis, and successfully treated a patient with irbesartan, an antihypertensive drug, resulting in a profound and durable response. Analysis showed an increase in immune signaling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumor, suggesting an activated immune response contributed to the anti-tumor effect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Cristina Lopez, Nikolai Schleussner, Stephan H. Bernhart, Kortine Kleinheinz, Stephanie Sungalee, Henrike L. Sczakiel, Helene Kretzmer, Umut H. Toprak, Selina Glaser, Rabea Wagener, Ole Ammerpohl, Susanne Bens, Maciej Giefing, Juan C. Gonzalez Sanchez, Gordana Apic, Daniel Huebschmann, Martin Janz, Markus Kreuz, Anja Mottok, Judith M. Mueller, Julian Seufert, Steve Hoffmann, Jan O. Korbel, Robert B. Russell, Roland Schuele, Lorenz Truemper, Wolfram Klapper, Bernhard Radlwimmer, Peter Lichter, Ralf Kueppers, Matthias Schlesner, Stephan Mathas, Reiner Siebert
Summary: Histone methylation-modifiers, including EZH2 and KMT2D, are frequently altered in B-cell lymphomas. In this study, we examined the whole genome and transcriptome data of 186 cases and identified recurrent alterations in KDM4C, a histone demethylase encoding gene on chromosome 9p24. We demonstrated that these structural variants in KDM4C result in loss-of-function and provide evidence that KDM4C can act as a tumor suppressor. Thus, our findings expand the mutational landscape of lymphomas and highlight the importance of KDM4C in B-cell derived lymphomas.