Article
Oncology
Gabrielle Leclercq, Helene Haegel, Alberto Toso, Tina Zimmermann, Luke Green, Nathalie Steinhoff, Johannes Sam, Vesna Pulko, Anneliese Schneider, Anna Maria Giusti, John Challier, Anne Freimoser-Grundschober, Laurent Lariviere, Alex Odermatt, Martin Stern, Pablo Umana, Marina Bacac, Christian Klein
Summary: This study aimed to identify small molecules that can reduce cytokine release while maintaining T cell-mediated tumor killing. By screening a library of FDA-approved kinase inhibitors, mTOR, JAK, and Src kinase inhibitors were found to modulate cytokine release. Further in vitro and in vivo experiments confirmed these findings and supported the evaluation of these inhibitors as a treatment to prevent cytokine release syndrome (CRS).
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Yuanwang Pan, Yuan Hao, Han Han, Ting Chen, Hailin Ding, Kristen E. Labbe, Elaine Shum, Kayla Guidry, Hai Hu, Fiona Sherman, Ke Geng, Janaye Stephens, Alison Chafitz, Sittinon Tang, Hsin-Yi Huang, Chengwei Peng, Christina Almonte, Jared E. Lopes, Heather C. Losey, Raymond J. Winquist, Vamsidhar Velcheti, Hua Zhang, Kwok-Kin Wong
Summary: The study demonstrated that mNemvaleukin significantly inhibited SCLC tumor growth, with the most significant survival benefit observed when combined with chemotherapy. mNemvaleukin expanded tumor-infiltrating NK cells and CD8(+) T cells, and promoted their activation and proliferation. Combining mNemvaleukin with chemotherapy had the strongest effects in activating effector and cytotoxic CD8(+) T cells.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Dentistry, Oral Surgery & Medicine
Nidhi Medara, Jason C. Lenzo, Katrina A. Walsh, Neil M. O'Brien-Simpson, Eric C. Reynolds, Ivan B. Darby
Summary: This study evaluated the longitudinal variation in peripheral T helper cells in periodontitis patients undergoing management, indicating potential roles of IFN-gamma(+) and Foxp3(+) cells in the systemic compartment of periodontitis. Treatment outcomes were associated with changes in the expression of IFN-gamma and Foxp3 cells. Periodontal management has local and systemic effects, highlighting the importance of assessing and managing periodontitis for overall systemic health.
JOURNAL OF CLINICAL PERIODONTOLOGY
(2021)
Review
Cell Biology
Hafid Ait-Oufella, Jean-Remi Lavillegrand, Alain Tedgui
Summary: Research shows that chronic inflammation triggered by cholesterol-rich lipoproteins is crucial in atherosclerosis development. Effector Th1 cells are proatherogenic, while regulatory T cells (Tregs) protect against atherosclerosis. Understanding how Tregs affect atherosclerosis could lead to new targeted therapies against cardiovascular disease.
Review
Cell Biology
David A. Lewis, Tony Ly
Summary: CD8(+) T cells are crucial in immunity and immuno-oncology, as they undergo complex cellular growth, cell cycle entry, and differentiation to produce antigen-specific cytotoxic T lymphocytes. Some activated T cells will differentiate into memory T cells which are essential in adaptive immunity. This review explores the control of cell cycle entry in CD8(+) T cells and the interaction between these mechanisms and pathways regulating immunological phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Valentina Rubino, Anna Teresa Palatucci, Giuliana La Rosa, Angela Giovazzino, Francesco Aruta, Simona Damiano, Flavia Carriero, Mariarosaria Santillo, Rosa Iodice, Paolo Mondola, Giuseppina Ruggiero, Giuseppe Terrazzano
Summary: Reactive oxygen species (ROS) play a role in T-cell activation, with SOD-1 production and secretion influenced by antigen-dependent activation. In patients with MS, SOD-1 levels are associated with T cell function and regulatory T cell populations, impacting cytokine secretion.
Article
Oncology
Rosemina Merchant, Carole Galligan, Manjunatha Ankathatti Munegowda, L. Bruce Pearce, Peter Lloyd, Paul Smith, Fahar Merchant, Minh D. To
Summary: MDNA11 is a next generation long-acting IL-2 immunotherapeutic that overcomes the limitations of current treatments by modifying receptor selectivity and extending the pharmacokinetic profile. It has been shown to control tumor growth and induce durable tumor clearance when used as a monotherapy or in combination with immune checkpoint inhibitors. Evaluation of MDNA11 in non-human primates demonstrates its good tolerability and the ability to stimulate a strong and durable immune response.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Takeshi Kawabe, Thomas Ciucci, Kwang Soon Kim, Shunichi Tayama, Akihisa Kawajiri, Takumi Suzuki, Riou Tanaka, Naoto Ishii, Dragana Jankovic, Jinfang Zhu, Jonathan Sprent, Remy Bosselut, Alan Sher
Summary: In this study, using single-cell RNA sequencing and flow cytometry, we identified distinct subsets within self-driven MP CD4(+) T lymphocytes and found that they differ from conventional foreign Ag-specific memory cells in marker expression and functional relevance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Dansen Wu, Liming Wang, Donghuang Hong, Caifa Zheng, Yongping Zeng, Huolan Ma, Jing Lin, Jialong Chen, Ronghui Zheng
Summary: Cytokines play a crucial role in the progression of sepsis, and IL-35 forms a network with other cytokines during the acute phase of sepsis, strongly affecting disease severity.
CLINICAL IMMUNOLOGY
(2022)
Article
Allergy
Hui Li, Huaqi Wang, Leon Sokulsky, Shaoxia Liu, Rui Yang, Xiaojie Liu, Lujia Zhou, Juan Li, Chun Huang, Fangfang Li, Xu Lei, Hongxia Jia, Jiuling Cheng, Fuguang Li, Ming Yang, Guojun Zhang
Summary: This study identified significantly elevated levels of monocytes, CD8(+) T cells, and macrophages in the bronchoalveolar lavage fluid of patients with asthma exacerbation. Additionally, a complicated molecular framework involving a set of cytokines and intracellular transduction regulators shared across multiple cell clusters was discovered. Moreover, core exacerbation-associated modules activated included pathways such as eukaryotic initiation factor 2 signaling and C-X-C chemokine receptor type 4 signaling in specific cell populations associated with infection.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Antonio Sorrentino, Ayse Nur Menevse, Tillmann Michels, Valentina Volpin, Franziska Christine Durst, Julian Sax, Maria Xydia, Abir Hussein, Slava Stamova, Steffen Spoerl, Nicole Heuschneider, Jasmin Muehlbauer, Katharina Marlene Jeltsch, Anchana Rathinasamy, Melanie Werner-Klein, Marco Breinig, Damian Mikietyn, Christian Kohler, Isabel Poschke, Sabrina Purr, Olivia Reidell, Catarina Martins Freire, Rienk Offringa, Claudia Gebhard, Rainer Spang, Michael Rehli, Michael Boutros, Christian Schmidl, Nisit Khandelwal, Philipp Beckhove
Summary: This study reveals a molecular mechanism that protects tumor cells from cytotoxic T-cell attack and demonstrates the feasibility of pharmacological inhibition of this pathway.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Kevin Dang, Giulia Castello, Starlynn C. Clarke, Yuping Li, Aarti Balasubramani, Andrew Boudreau, Laura Davison, Katherine E. Harris, Duy Pham, Preethi Sankaran, Harshad S. Ugamraj, Rong Deng, Serena Kwek, Alec Starzinski, Suhasini Iyer, Wim van Schooten, Ute Schellenberger, Wenchao Sun, Nathan D. Trinklein, Roland Buelow, Ben Buelow, Lawrence Fong, Pranjali Dalvi
Summary: TNB-585, an anti-CD3xPSMA TCE, shows promising efficacy in vitro in inducing activation and proliferation of human T cells, killing PSMA(+) prostate tumor cells, and reducing cytokine release and regulatory T cell activation. In addition, TNB-585 demonstrates potent efficacy against patient-derived prostate tumors ex vivo and in vivo, suggesting it may be a promising therapy for mCRPC with lower incidence and severity of CRS compared to TCEs with high-affinity anti-CD3 domains.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Gabrielle Leclercq, Helene Haegel, Anneliese Schneider, Anna Maria Giusti, Estelle Marrer-Berger, Christophe Boetsch, Antje-Christine Walz, Vesna Pulko, Johannes Sam, John Challier, Cristiano Ferlini, Alex Odermatt, Pablo Umana, Marina Bacac, Christian Klein
Summary: The study demonstrates that dasatinib can effectively serve as a pharmacological on/off switch to mitigate off-tumor toxicities or CRS induced by T cell bispecific antibodies. By providing pharmacologically relevant doses, dasatinib can regulate T cell activation, cell killing, and cytokine release triggered by T cell engagers.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Cell Biology
Adrian A. Naoun, Itay Raphael, Thomas G. Forsthuber
Summary: Quorum sensing is not limited to bacteria, but may also play an important role in the mammalian immune system. This article explores the quorum sensing-like mechanisms in the immune system, particularly in regulating T cell behavior. It also discusses the potential therapeutic implications of modulating immune system-related quorum sensing.
Review
Microbiology
Brigitta Stockinger
Summary: Infection with Citrobacter rodentium triggers a threat to the intestinal barrier, prompting a coordinated immune response involving Th17 cells to limit bacterial translocation and repair damaged epithelium with the aid of environmental factors.
CURRENT OPINION IN MICROBIOLOGY
(2021)
Article
Immunology
Marwah M. Albakri, Frank A. Veliz, Steven N. Fiering, Nicole F. Steinmetz, Scott F. Sieg
Article
Immunology
Scott F. Sieg, Douglas A. Bazdar, David Zidar, Michael Freeman, Michael M. Lederman, Nicholas T. Funderburg
Article
Immunology
Bonnie Chen, Stephen R. Morris, Soumya Panigrahi, Gillian M. Michaelson, Jonathan M. Wyrick, Alexey A. Komissarov, Daria Potashnikova, Anna Lebedeva, Souheil-Antoine Younes, Karem Harth, Vikram S. Kashyap, Elena Vasilieva, Leonid Margolis, David A. Zidar, Scott F. Sieg, Carey L. Shive, Nicholas T. Funderburg, Sara Gianella, Michael M. Lederman, Michael L. Freeman
JOURNAL OF IMMUNOLOGY
(2020)
Article
Immunology
Soumya Panigrahi, Douglas A. Bazdar, Marwah Albakri, Brian Ferrari, Christopher J. Antonelli, Michael L. Freeman, George Dubyak, Chad Zender, Scott F. Sieg
EUROPEAN JOURNAL OF IMMUNOLOGY
(2020)
Article
Medicine, Research & Experimental
Stephen R. Morris, Bonnie Chen, Joseph C. Mudd, Soumya Panigrahi, Carey L. Shive, Scott F. Sieg, Cheryl M. Cameron, David A. Zidar, Nicholas T. Funderburg, Souheil-Antoine Younes, Benigno Rodriguez, Sara Gianella, Michael M. Lederman, Michael L. Freeman
Article
Microbiology
Emily R. Bowman, Cheryl M. Cameron, Brian Richardson, Manjusha Kulkarni, Janelle Gabriel, Morgan J. Cichon, Kenneth M. Riedl, Yousef Mustafa, Michael Cartwright, Brandon Snyder, Subha V. Raman, David A. Zidar, Susan L. Koletar, Martin P. Playford, Nehal N. Mehta, Scott F. Sieg, Michael L. Freeman, Michael M. Lederman, Mark J. Cameron, Nicholas T. Funderburg
Article
Infectious Diseases
Scott F. Sieg, Carey L. Shive, Soumya Panigrahi, Michael L. Freeman
Summary: Recent studies have shown that factors such as anti-retroviral therapy, co-infections, immune system alterations, and microbiome perturbations contribute to HIV-associated inflammation, potentially increasing the risk of age-related morbidities in people living with HIV. Understanding the mechanisms that exacerbate inflammaging in people with HIV may lead to improved intervention strategies, ultimately extending both lifespan and healthspan.
CURRENT HIV/AIDS REPORTS
(2021)
Article
Immunology
Eileen P. Scully, Evgenia Aga, Athe Tsibris, Nancie Archin, Kate Starr, Qing Ma, Gene D. Morse, Kathleen E. Squires, Bonnie J. Howell, Guoxin Wu, Lara Hosey, Scott F. Sieg, Lynsay Ehui, Francoise Giguel, Kendyll Coxen, Curtis Dobrowolski, Monica Gandhi, Steve Deeks, Nicolas Chomont, Elizabeth Connick, Catherine Godfrey, Jonathan Karn, Daniel R. Kuritzkes, Ronald J. Bosch, Rajesh T. Gandhi
Summary: Combination therapy with tamoxifen and vorinostat did not augment HIV latency reversal over vorinostat alone in postmenopausal women. Histone acetylation changes were associated with HIV RNA induction. Enrollment of postmenopausal women in interventional trials of cure strategies is feasible.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Microbiology
Soumya Panigrahi, Tamal Goswami, Brian Ferrari, Christopher J. Antonelli, Douglas A. Bazdar, Hannah Gilmore, Michael L. Freeman, Michael M. Lederman, Scott F. Sieg
Summary: SARS-CoV-2 infection leads to reduced ACE2 expression on cells, potentially causing compromised respiratory function and thrombotic events. Increased levels of molecules like angiotensin II and bradykinin may contribute to inflammation, while spike protein and bradykinin can induce dysfunction in endothelial cells.
MICROBIOLOGY SPECTRUM
(2021)
Article
Cell Biology
Marwah M. Albakri, Stanley Ching-Cheng Huang, Hammad N. Tashkandi, Scott F. Sieg
Summary: The study demonstrates that fatty acids derived from tumor cells can mediate the maturation of macrophages into a cell type with limited pro-inflammatory characteristics, as indicated by experiments with supernatants.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Soumya Panigrahi, Santosh K. Ghosh, Brian Ferrari, Jonathan M. Wyrick, Eugene A. Podrez, Aaron Weinberg, Scott F. Sieg
Summary: This study demonstrates that human platelets and megakaryocytes contain an important antimicrobial peptide called hBD-3, which can be detected on the surface of activated platelets as well as in platelet derived extracellular vesicles (p-EVs). The presence of hBD-3 in p-EVs can contribute to platelet activation and endothelial dysfunction, potentially creating a pro-thrombotic vascular microenvironment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Microbiology
Manish C. Choudhary, Kara W. Chew, Rinki Deo, James P. Flynn, James Regan, Charles R. Crain, Carlee Moser, Michael D. Hughes, Justin Ritz, Ruy M. Ribeiro, Ruian Ke, Joan A. Dragavon, Arzhang Cyrus Javan, Ajay Nirula, Paul Klekotka, Alexander L. Greninger, Courtney Fletcher, Eric S. Daar, David A. Wohl, Joseph J. Eron, Judith S. Currier, Urvi M. Parikh, Scott F. Sieg, Alan S. Perelson, Robert W. Coombs, Davey M. Smith, Jonathan Z. Li
Summary: This article reports the emergence of SARS-CoV-2 escape mutations during bamlanivimab therapy in a phase II clinical trial. The study found that treatment-emergent resistance mutations were more likely to be detected in the low-dose treatment group, and participants with resistance mutations had higher respiratory tract viral loads. The results also showed the rapid replication of the virus after the emergence of resistance mutations.
NATURE MICROBIOLOGY
(2022)
Article
Medicine, General & Internal
Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E. Milliren, Carolyn S. Calfee, Charles B. Cairns, Monica Kraft, Lindsey R. Baden, Albert C. Shaw, Florian Krammer, Harm van Bakel, Denise A. Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Ofer Levy, Christian Bime, Elias K. Haddad, David J. Erle, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Catherine L. Hough, William B. Messer, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Mark A. Atkinson, Scott C. Brakenridge, David Corry, Farrah Kheradmand, Lauren I. R. Ehrlich, Esther Melamed, Grace A. McComsey, Rafick Sekaly, Joann Diray-Arce, Bjoern Peters, Alison D. Augustine, Elaine F. Reed, Matthew C. Altman, Patrice M. Becker, Nadine Rouphael, IMPACC Study Grp
Summary: This study aims to better understand the association between characteristics of COVID-19 patients and their outcomes. It found that risk factors such as age, Hispanic ethnicity, elevated baseline creatinine or troponin levels, baseline lymphopenia, presence of infiltrate by chest imaging, and high SARS-CoV2 viral load were associated with prolonged hospitalization or death. Female sex was the only risk factor associated with post-acute sequalae of COVID-19 (PASC). The findings provide important insights for patient management and prognosis improvement.
Article
Immunology
Carlee Moser, Jonathan Z. Li, Joseph J. Eron, Evgenia Aga, Eric S. Daar, David A. Wohl, Robert W. Coombs, Arzhang Cyrus Javan, Rachel A. Bender Ignacio, Prasanna Jagannathan, Justin Ritz, Scott F. Sieg, Urvi M. Parikh, Michael D. Hughes, Judith S. Currier, Davey M. Smith, Kara W. Chew
Summary: This study found that SARS-CoV-2 RNA shedding is consistent across different compartments. Age is strongly associated with viral shedding, and men have slower viral clearance, which may explain gender differences in acute COVID-19 outcomes.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Article
Medicine, Research & Experimental
Sydney I. Ramirez, Alba Grifoni, Daniela Weiskopf, Urvi M. Parikh, Amy Heaps, Farhoud Faraji, Scott F. Sieg, Justin Ritz, Carlee Moser, Joseph J. Eron, Judith S. Currier, Paul Klekotka, Alessandro Sette, David A. Wohl, Eric S. Daar, Michael D. Hughes, Kara W. Chew, Davey M. Smith, Shane Crotty
Summary: This study compared the T cell responses of COVID-19 patients treated with bamlanivimab or placebo and found that bamlanivimab did not affect the quantity and quality of SARS-CoV-2-specific T cell memory. This suggests that patients receiving this treatment can still generate effective immune memory.