Article
Medicine, Research & Experimental
Meredith L. Stone, Jesse Lee, Veronica M. Herrera, Kathleen Graham, Jae W. Lee, Austin Huffman, Heather Coho, Evan Tooker, Max Myers, Michael Giannone, Yan Li, Thomas H. Buckingham, Kristen B. Long, Gregory L. Beatty
Summary: Agonist CD40 antibodies in combination with chemotherapy can lead to systemic cytokine release, liver transaminase elevations, and chemotherapy-induced hepatotoxicity. However, neutralization of TNF can mitigate liver sensitivity to toxicity induced by anti-CD40, without affecting antitumor efficacy.
Review
Cell Biology
Carlotta Cattolico, Peter Bailey, Simon T. Barry
Summary: Pancreatic ductal adenocarcinomas (PDAC) have poor responses to immunotherapy due to immunosuppressive tumor microenvironment and low infiltration of tumor CD8(+) T cells. However, alterations in tumor DNA and chemotherapy can activate immune cells, but defects in immune-sensing mechanisms in PDAC limit the effectiveness of immunotherapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Damien J. Zanker, Katie L. Owen, Nikola Baschuk, Alex J. Spurling, Belinda S. Parker
Summary: This study underscores the importance of intact type I IFN signaling to NK cells in the regulation of tumorigenesis and metastasis, and suggests that the IFNAR status on NK cells should be considered when devising therapeutic strategies aimed at inducing systemic type I IFN signaling in breast cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Khiem C. Lam, Romina E. Araya, April Huang, Quanyi Chen, Martina Di Modica, Richard R. Rodrigues, Amelie Lopes, Sarah B. Johnson, Benjamin Schwarz, Eric Bohrnsen, Alexandria P. Cogdill, Catharine M. Bosio, Jennifer A. Wargo, Maxwell P. Lee, Romina S. Goldszmid
Summary: This study reveals how the microbiota influences the immune components of the TME to improve cancer therapy. Modulating the microbiota can trigger the IFN-I-NK cell-DC axis within tumors, enhancing the efficacy of immune checkpoint blockade (ICB).
Article
Oncology
Weijian Wu, Huiying Xu, Chenyang Liao, Youqiao Wang, Ruirui Wu, Jiaxin Wu, Wenlv Zheng, Yunzhi Li, Chaoying Jin, Yuxuan Zhao, Junmin Quan, Xin Yue, Xianzhang Bu
Summary: This study reveals that USP14 is one of the major suppressors of IFN production and impairs the activation of IRF3. Blockade of USP14 enhances STING signaling activation and promotes radiation-induced adaptive immune responses.
Article
Gastroenterology & Hepatology
Wei Si, Hua Liang, Jason Bugno, Qi Xu, Xingchen Ding, Kaiting Yang, Yanbin Fu, Ralph R. Weichselbaum, Xin Zhao, Liangliang Wang
Summary: Our study demonstrates that oral administration of live LGG enhances the antitumour activity of anti-PD-1 immunotherapy by increasing tumour-infiltrating DCs and T cells, and by shifting the gut microbial community towards enrichment in Lactobacillus murinus and Bacteroides uniformis. Mechanistically, LGG induces IFN-beta production via the cGAS/STING/TBK1/IRF7 axis in DCs, highlighting the potential of LGG as a combination agent with ICB for cancer therapies.
Article
Oncology
Shannon Lange, Laurens G. L. Sand, Matthew Bell, Sagar L. Patil, Deanna Langfitt, Stephen Gottschalk
Summary: We designed a chimeric cytokine receptor (GM18) that links CAR T-cell activation to MyD88 signaling. GM18 endows CAR T cells with sustained effector function in the setting of chronic antigen exposure, resulting in potent antitumor activity in preclinical solid tumor models.
Article
Oncology
Kyoko Nakamura, Ankur Karmokar, Paul M. Farrington, Neil H. James, Antonio Ramos-Montoya, Susan J. Bickerton, Gareth D. Hughes, Timothy M. Illidge, Elaine B. Cadogan, Barry R. Davies, Simon J. Dovedi, Viia Valge-Archer
Summary: The combination of AZD7648 with radiotherapy induced complete tumor regressions in a significant proportion of mice, dependent on CD8T cells and modulating an anticancer immune response. Immunological consequences included a reduction in T-cell PD-1 expression, increased NK-cell granzyme B expression, and elevated type I IFN signaling.
CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Akshay J. Patel, Zena N. Willsmore, Naeem Khan, Alex Richter, Babu Naidu, Mark T. Drayson, Sophie Papa, Andrew Cope, Sophia N. Karagiannis, Esperanza Perucha, Gary W. Middleton
Summary: Checkpoint blockade with Pembrolizumab has proven effective in treating advanced non-small cell lung cancer. However, some patients experience high-grade immune related adverse events (irAEs) during treatment. This study reveals that a deficient Breg checkpoint fails to control self-reactive T cell activity and auto-antibody formation in these patients, leading to severe auto-inflammatory sequelae. Pre-therapy B cell profiling may help identify patients at high risk of developing severe irAEs.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Renren Yu, Bo Zhu, Degao Chen
Summary: Type I interferons inhibit tumor growth directly and indirectly by acting upon tumor and immune cells, with evidence showing that enhancing both endo- and exogenously produced type I IFNs have a synergistic effect on anti-tumor immunity. Clinical trials are currently exploring new treatment strategies combining type I IFN inducers with ICBs, highlighting the importance of understanding the cellular sources and roles of type I IFNs in the immune regulation of the tumor microenvironment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Immunology
Hong-Yan Chen, Rong-Chun Tang, Jia-Wei Liang, Weijia Zhao, Shuang-Shuang Yu, Rui Xu, Ao Zhang, Shijin Geng, Xiu-Yuan Sun, Qing Ge, Jun Zhang
Summary: In this study, a novel negative regulator of the immune system, USP47, was discovered. By removing K63-linked polyubiquitin chains from TRAF3 and TRAF6, USP47 inhibits type I IFN signaling, leading to reduced antiviral immune responses.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Microbiology
Jian Wang, Hui Zheng, Chunsheng Dong, Sidong Xiong
Summary: This study identifies a human deubiquitinase, OTUD6B, as a positive regulator of IRF3-mediated antiviral immune response. OTUD6B enhances cellular antiviral responses and overexpression of OTUD6B in mice increases resistance to RNA virus infection.
Review
Immunology
Yinghong Wang, Robert R. Jenq, Jennifer A. Wargo, Stephanie S. Watowich
Summary: The microbiome plays a role in immunotherapy and its associated adverse events. Wang, Jenq, et al. discuss the microbiome's influence on immune-related adverse events (irAEs) by examining bacterial taxa, immune mechanisms, and clinical opportunities for modulating the microbiome to treat irAEs.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Lilv Fan, Guiliang Xu, Jingjing Cao, Min Li, Huihui Zhang, Fanlin Li, Xinyue Qi, Xiaoqing Zhang, Zeyu Li, Ping Han, Xuanming Yang
Summary: This study found that IFNa can directly inhibit the progression of CRPC, reduce the number of G-MDSCs in the tumor microenvironment, and weaken their inhibitory function on T cell activation, providing a potential strategy for the clinical treatment of CRPC.
Review
Immunology
Michael Karin, Shabnam Shalapour
Summary: Chronic inflammation promotes tumor development and treatment resistance, while the antagonism between inflammation and immunity, as well as cancer cells' ability to evade immune detection, affect cancer development and treatment outcomes.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Letter
Allergy
Derek K. Chu, Joseph L. Baumert, Steve L. Taylor, Julie A. Nordlee, Tina Nham, Jonathan Bramson, Sebastien La Vieille, Michael A. Abbott, Paul Spill, Andrea Marrin, Manel Jordana, Susan Waserman
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Cell & Tissue Engineering
Ksenia Bezverbnaya, Duane Moogk, Derek Cummings, Christopher L. Baker, Craig Aarts, Galina Denisova, Michael Sun, Jamie D. McNicol, Rebecca C. Turner, Anthony F. Rullo, S. Ronan Foley, Jonathan L. Bramson
Summary: The researchers have optimized a next-generation TAC receptor for T cell engineering, using a novel structure to enhance surface expression and efficacy, with the technology maintaining therapeutic efficacy regardless of expression levels.
Article
Multidisciplinary Sciences
Ana L. Portillo, Richard Hogg, Sophie M. Poznanski, Eduardo A. Rojas, Niamh J. Cashell, Joanne A. Hammill, Marianne Chew, Mira M. Shenouda, Tyrah M. Ritchie, Quynh T. Cao, Jeremy A. Hirota, Sukhbinder Dhesy-Thind, Jonathan L. Bramson, Ali A. Ashkar
Summary: The study shows that HER2 CAR-NK cells enhance anti-tumor functions against HER2-expressing cancer cells without affecting non-malignant cells, suggesting a promising and safe immunotherapy option for solid tumors.
Article
Oncology
Donald J. Bastin, Gillian Mount, Cyrus C. Hsia, Mohammad Jarrar, Kit McCann, Anargyros Xenocostas, Anouar Teriaky, Uday Deotare
HEMATOLOGY TRANSFUSION AND CELL THERAPY
(2023)
Review
Cell & Tissue Engineering
Donald J. Bastin, Jennifer Quizi, Michael A. Kennedy, Natasha Kekre, Rebecca C. Auer
Summary: Autologous whole cell vaccines show potential and favorable safety profile in treating hematological cancers. However, manufacturing challenges hinder their efficacy and clinical implementation. This literature review defines the key issues in manufacturing autologous whole cell products and provides a summary of pre-clinical work on overcoming these challenges.
Article
Oncology
Housne Begum, Anand Swaminath, Yung Lee, Christine Fahim, Jonathan Bramson, Asghar Naqvi, Yaron Shargall, Christian Finley, Wael Hanna, John Agzarian
Summary: This study aims to assess the effectiveness of SBRT on reducing tumor viability in patients with pulmonary metastases. The study will evaluate the use of dual treatment with neoadjuvant SBRT followed by surgical resection, and analyze outcomes such as complete pathologic response, overall survival, and disease-free survival.
TRANSLATIONAL CANCER RESEARCH
(2022)
Article
Endocrinology & Metabolism
Lindsay A. Broadfield, Amna Saigal, Jake C. Szamosi, Joanne A. Hammill, Ksenia Bezverbnaya, Dongdong Wang, Jaya Gautam, Evangelia E. Tsakiridis, Fiorella Di Pastena, Jamie McNicol, Jianhan Wu, Saad Syed, James S. V. Lally, Amogelang R. Raphenya, Marie-Jose Blouin, Michael Pollak, Andrea Sacconi, Giovanni Blandino, Andrew G. McArthur, Jonathan D. Schertzer, Michael G. Surette, Stephen M. Collins, Jonathan L. Bramson, Paola Muti, Theodoros Tsakiridis, Gregory R. Steinberg
Summary: This study demonstrates that in obese mice fed a high-fat diet, metformin reduces tumor burden through changes in the gut microbiome. Fecal microbiome transfer or in vitro treatment with fecal filtrates from high-fat diet-fed animals partially recapitulates the acceleration of tumor growth. Oral administration of metformin suppresses tumor growth and increases the expression of short-chain fatty acid-producing microbes. Transplanting the gut microbiome from mice treated orally with metformin to drug naive obese mice reduces tumor proliferation and affects the expression of tumor-related genes.
MOLECULAR METABOLISM
(2022)
Article
Immunology
Jessica A. Breznik, Angela Huynh, Ali Zhang, Lucas Bilaver, Hina Bhakta, Hannah D. Stacey, Jann C. Ang, Jonathan L. Bramson, Ishac Nazy, Matthew S. Miller, Judah Denburg, Andrew P. Costa, Dawn M. E. Bowdish, Eric D. Brown, Gerry Wright, David C. Bulir, Mark Loeb, Marek Smieja, Aaron Jones, Parminder Raina, Chris Verschoor, Janet E. McElhaney, Kevin Brown, George A. Heckman, John P. Hirdes, Michael P. Hillmer, Ahmad Von Schlegell, Nathan M. Stall, Kevin Stinson, Arthur Sweetman
Summary: Chronic infection with human CMV does not affect antibody levels and quality, as well as cellular memory recall responses, after SARS-CoV-2 mRNA vaccination in older adults. However, CMV seropositivity may alter T cell composition without impeding the durability of humoral protection or cellular memory responses.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell & Tissue Engineering
Arya Afsahi, Rebecca Burchett, Christopher L. Baker, Allyson E. Moore, Jonathan L. Bramson
Summary: We engineered T cells to express recombinant single-chain IL-27 and a synthetic antigen receptor, and found that IL-27-expressing T cells sustained anti-tumor immunity and cytotoxicity while reducing pro-inflammatory cytokines. IL-27-expressing T cells may provide a potential avenue to avoid treatment-related toxicities commonly associated with engineered T-cell therapy.
Article
Cell & Tissue Engineering
Ksenia Bezverbnaya, Joanne A. Hammill, Derek Cummings, Bojana Bojovic, Bella Groisman, Christopher L. Baker, Craig Aarts, Danielle L. Hayes, Donna Rill, Stacey X. Xu, Andreas G. Bader, Christopher W. Helsen, Jonathan L. Bramson
Summary: B-cell maturation antigen (BCMA) is a clinically validated target for multiple myeloma. The authors have developed a fully humanized BCMA-specific T-cell antigen coupler (TAC) receptor. Optimization of the BCMA-specific TAC receptor was achieved through iterations of the BCMA-TAC design.
Article
Multidisciplinary Sciences
Donald J. J. Bastin, Joshua Montroy, Michael A. A. Kennedy, Andre B. B. Martel, Risa Shorr, Maryam Ghiasi, Dominique M. M. Boucher, Boaz Wong, Louise Gresham, Jean-Simon Diallo, Dean A. A. Fergusson, Manoj M. M. Lalu, Natasha Kekre, Rebecca C. C. Auer
Summary: We conducted a systematic review and meta-analysis to assess the safety and efficacy of autologous whole cell vaccines for solid tumors. The study found that the vaccines were well tolerated with few adverse events, and showed improvement in overall and disease-free survival rates. The results suggest that autologous whole cell vaccination is a safe and effective treatment for solid tumors.
SCIENTIFIC REPORTS
(2023)
Article
Immunology
Arya Afsahi, Christopher M. M. Silvestri, Allyson E. E. Moore, Carly F. F. Graham, Kaylyn Bacchiochi, Martine St-Jean, Christopher L. L. Baker, Robert G. G. Korneluk, Shawn T. T. Beug, Eric C. C. LaCasse, Jonathan L. L. Bramson
Summary: The SMAC mimetic drug LCL161 enhances T cell function by inhibiting IAP proteins and activating the non-canonical NF-kappa B pathway. However, LCL161 does not improve T cell anti-tumor function when interacting with myeloma cells, possibly due to sensitization of T cells to Fas-mediated apoptosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Geriatrics & Gerontology
Jessica A. Breznik, Ahmad Rahim, Tara Kajaks, Megan Hagerman, Lucas Bilaver, Karen Colwill, Roaya M. Dayam, Anne -Claude Gingras, Chris P. Verschoor, Janet E. McElhaney, Jonathan L. Bramson, Dawn M. E. Bowdish, Andrew P. Costa
Summary: A longitudinal cohort study in nursing and retirement homes in Ontario, Canada, identified vaccine type, number of doses, and recent infection history as important factors for protection against Omicron variant infection in older adults.
JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION
(2023)
Article
Education, Scientific Disciplines
Max Deschner, Donald J. Bastin, Ziad Solh, Karen Bosma, Wael Haddara, Ping Yang, Robert Broadbent, Aaron Haig, Jonathan Keow, Mayur Brahmania, Anargyros Xenocostas, Uday Deotare
Summary: Graft-versus-host disease is a rare but deadly complication of solid organ transplant with non-specific clinical features. Prompt diagnosis and management are crucial for improving patient survival.
Article
Oncology
Seung Mi Yoo, Vivan W. C. Lau, Craig Aarts, Bojana Bojovic, Gregory Steinberg, Joanne A. Hammill, Anna Dvorkin-Gheva, Raja Ghosh, Jonathan L. Bramson
Summary: Engineered T cell products manufactured within a HFMBR showed greater therapeutic potency and increased resistance to cryopreservation compared to traditional manual methods. This was associated with changes in programming towards glycolytic metabolism. The choice of bioreactor for manufacturing T cell products can fundamentally impact the therapeutic potential of the final product.