Article
Biochemistry & Molecular Biology
Priska Jost, Franziska Klein, Benjamin Brand, Vanessa Wahl, Amanda Wyatt, Daniela Yildiz, Ulrich Boehm, Barbara A. A. Niemeyer, Martin Vaeth, Dalia Alansary
Summary: Mitochondria play a crucial role in modulating T cell function through their control of energy production and Ca2+ homeostasis. The mitochondrial Ca2+ uniporter (MCU) regulates Ca2+ signals and affects T cell activation. However, the specific effects of MCU on regulatory CD4 T cells (Treg) and their suppressive potential are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Beth E. Grace, Coralie M. Backlund, Duncan M. Morgan, Byong H. Kang, Nishant K. Singh, Brooke D. Huisman, C. Garrett Rappazzo, Kelly D. Moynihan, Laura Maiorino, Connor S. Dobson, Taeyoon Kyung, Khloe S. Gordon, Patrick Holec, Overbeck C. Takou Mbah, Daniel Garafola, Shengwei Wu, J. Christopher Love, K. Dane Wittrup, Darrell J. Irvine, Michael E. Birnbaum
Summary: This study characterized the CD8(+) T cell response to melanoma, identified a dominant tumor-associated antigen, and generated mimotopes that induced robust functional T cell responses with cross-reactivity to the endogenous antigen.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Feng Shan, Anthony R. Cillo, Carly Cardello, Daniel Y. Yuan, Sheryl R. Kunning, Jian Cui, Caleb Lampenfeld, Asia M. Williams, Alexandra P. Mcdonough, Arjun Pennathur, James D. Luketich, John M. Kirkwood, Robert L. Ferris, Tullia C. Bruno, Creg J. Workman, Panayiotis V. Benos, Dario A. A. Vignali
Summary: Research identified an activated Tregs subpopulation expressing multiple tumor necrosis factor receptor genes in head and neck squamous cell carcinoma tumors, associated with worse prognosis. The transcription factor BATF plays a central role in limiting excessive activation and promoting the survival of activated T-regs. Additionally, a suite of surface molecules reflective of the BATF-driven transcriptional network on intratumoral T-regs was identified.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Cameron W. Paterson, Melissa B. Gutierrez, Craig M. Coopersmith, Mandy L. Ford
Summary: Chronic alcohol use leads to T cell dysregulation within the adaptive immune system. In this study, using a murine model, researchers compared rare splenic subpopulations in alcohol-exposed mice and water-fed controls. The results showed decreased naive T cell populations and alterations in effector regulatory T cell phenotypes in chronic alcohol-induced immune dysfunction.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Giacomo Oliveira, Kari Stromhaug, Nicoletta Cieri, J. Bryan Iorgulescu, Susan Klaeger, Jacquelyn O. Wolff, Suzanna Rachimi, Vipheaviny Chea, Kate Krause, Samuel S. Freeman, Wandi Zhang, Shuqiang Li, David A. Braun, Donna Neuberg, Steven A. Carr, Kenneth J. Livak, Dennie T. Frederick, Edward F. Fritsch, Megan Wind-Rotolo, Nir Hacohen, Moshe Sade-Feldman, Charles H. Yoon, Derin B. Keskin, Patrick A. Ott, Scott J. Rodig, Genevieve M. Boland, Catherine J. Wu
Summary: In this study, the phenotype and tumor specificity of CD4 (+) T cells infiltrating human melanoma specimens were analyzed in depth, revealing that melanoma cells can directly induce exhausted cytotoxic CD4 (+) T cells through recognition of HLA class II-restricted neoantigens and HLA class I-restricted tumor-associated antigens. CD4 (+) T regulatory (T-Reg) cells can be indirectly elicited through the presentation of tumor antigens via antigen-presenting cells. Interestingly, a large number of tumor-reactive CD4 (+) T-Reg clones were stimulated directly by HLA class II-positive melanoma and showed specificity for melanoma neoantigens. These findings suggest that the presentation of HLA class II-restricted neoantigens and direct engagement of immunosuppressive CD4 (+) T-Reg cells are favored mechanisms of immune evasion in HLA class II-positive melanoma.
Article
Oncology
Hemanth K. Potluri, Carolina A. Ferreira, Joseph Grudzinski, Christopher Massey, Eduardo Aluicio-Sarduy, Jonathan W. Engle, Ohyun Kwon, Ian R. Marsh, Bryan P. Bednarz, Reinier Hernandez, Jamey P. Weichert, Douglas G. McNeel
Summary: This study found that the combination of targeted radionuclide therapy (TRT) and PD-1 blockade therapy is ineffective in prostate cancer models due to the activating effect of anti-PD-1 on regulatory T cells (Tregs). The results emphasize the importance of understanding the effects of TRT and immunotherapy combinations on the tumor immune microenvironment before clinical investigation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Yasmin R. Mohseni, Adeel Saleem, Sim L. Tung, Caroline Dudreuilh, Cameron Lang, Qi Peng, Alessia Volpe, George Adigbli, Amy Cross, Joanna Hester, Farzin Farzaneh, Cristiano Scotta, Robert I. Lechler, Fadi Issa, Gilbert O. Fruhwirth, Giovanna Lombardi
Summary: This study demonstrates the enhanced specificity and suppressive capacity of engineered Tregs with HLA-A2 CAR, IL-10 expression, and an imaging reporter, providing a proof-of-principle for next-generation Treg therapy in transplantation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Review
Immunology
Meihong Da, Luxia Chen, Alexander Enk, Sabine Ring, Karsten Mahnke
Summary: Adenosine (Ado) has immunosuppressive effects, and the ectoenzyme CD73 is crucial for the production of extracellular Ado. CD73 is highly expressed in regulatory T cells (Tregs) and upregulated after activation. Ado generated by CD73(+) Tregs plays a role in immune suppression of dendritic cells, monocytes, and T cells, making CD73 a novel checkpoint inhibitor in immunosuppressive environments such as tumors. Therapeutic intervention targeting CD73 is currently under investigation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Ilse Gille, Frans H. J. Claas, Geert W. Haasnoot, Mirjam H. M. Heemskerk, Sebastiaan Heidt
Summary: Solid organ transplantation is an effective treatment for end-stage diseases, but the need for immunosuppression can lead to serious side effects. CAR Treg therapy, specifically with HLA-A2 CAR Tregs, shows potential in promoting transplantation tolerance and improving graft survival.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Min Hu, Natasha M. Rogers, Jennifer Li, Geoff Y. Zhang, Yuan Min Wang, Karli Shaw, Philip J. O'Connell, Stephen Alexander
Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biology
Yousra Ajouaou, Abdulkader Azouz, Anaelle Taquin, Sebastien Denanglaire, Hind Hussein, Mohammad Krayem, Fabienne Andris, Muriel Moser, Stanislas Goriely, Oberdan Leo
Summary: PHD2 plays an important role in regulating Treg phenotype and function. Deficiency of PHD2 in Tregs leads to systemic inflammatory syndrome and immune dysregulation, possibly due to the function of the PHD2-HIF2α axis.
Article
Immunology
Dandan Yang, Xueqiang Zhao, Xin Lin
Summary: Bcl10 plays a critical role in the development and function of regulatory T (Treg) cells, deficiency of which leads to impaired development and suppressive function of Treg cells, even causing lethal autoimmunity. Bcl10-deficient Treg cells can undergo conversion into proinflammatory cells and decrease in effector Treg cell populations. The study provides genetic evidence that Bcl10 is essential for Treg cell development and function.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Review
Immunology
Zhussipbek Mukhatayev, Yekaterina O. Ostapchuk, Deyu Fang, I. Caroline Le Poole
Summary: Regulatory T cells (Tregs) play a crucial role in autoimmune skin diseases, and alterations in their numbers and functions can lead to various conditions. The use of antigen-specific Tregs engineered cells shows promise in improving treatment efficacy, though challenges in clinical applications need to be addressed.
AUTOIMMUNITY REVIEWS
(2021)
Article
Neurosciences
Aaron D. Thome, Farah Atassi, Jinghong Wang, Alireza Faridar, Weihua Zhao, Jason R. Thonhoff, David R. Beers, Eugene C. Lai, Stanley H. Appel
Summary: In this study, a shift towards a pro-inflammatory peripheral immune response in patients with Parkinson's disease (PD) was identified, with the loss of suppressive functions of regulatory T cells (Tregs) being a significant contributing factor. Ex vivo expansion of Tregs restored and enhanced their suppressive functions, suggesting a potential cell therapeutic approach for patients with PD.
NPJ PARKINSONS DISEASE
(2021)
Article
Multidisciplinary Sciences
Nami Sato, Nozomu Sakai, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Shigetsugu Takano, Gaku Ohira, Hideaki Miyauchi, Hisahiro Matsubara, Masayuki Ohtsuka
Summary: This study reveals the importance of Smurf2 in colorectal cancer and liver metastases. High expression of Smurf2 is associated with better prognosis, while low expression is a predictor of poor prognosis. In vitro experiments demonstrate that knockdown of Smurf2 enhances cell migration and tumor sphere formation, as well as increases the expression of EpCAM. Therefore, Smurf2 can be considered as a positive biomarker of cancer stem cell-like properties.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Eva Perez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Smith, Sung Chin, Khiem C. Lam, Andres Thorkelsson, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Shyam K. Sharan, Terry Van Dyke, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino
Article
Immunology
Devin Dersh, James D. Phelan, Megan E. Gumina, Boya Wang, Jesse H. Arbuckle, Jaroslav Holly, Rigel J. Kishton, Tovah E. Markowitz, Mina O. Seedhom, Nathan Fridlyand, George W. Wright, Da Wei Huang, Michele Ceribelli, Craig J. Thomas, Justin B. Lack, Nicholas P. Restifo, Thomas M. Kristie, Louis M. Staudt, Jonathan W. Yewdell
Summary: Genome-wide screening in diffuse large B cell lymphomas identified genes that modulate MHC-I cell surface expression in multiple pathways. These genes represent potential targets for manipulating MHC-I immunosurveillance in cancers and other diseases. Pharmacological inhibition of negative regulators of antigen presentation enhanced MHC-I presentation in DLBCL.
Article
Oncology
Melinda L. Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R. Acharya, Kaitlin Zablotsky, Bernard A. Fox, Carlo B. Bifulco, Shawn M. Jensen, Carmen Ballesteros-Merino, Mai Hope Le, Robert H. Pierce, Erica Browning, Reneta Hermiz, Lauren Svenson, Donna Bannavong, Kim Jaffe, Jendy Sell, Kellie Malloy Foerter, David A. Canton, Christopher G. Twitty, Takuya Osada, H. Kim Lyerly, Erika J. Crosby
Summary: This study demonstrates that Tavo treatment can enhance the CXCR3 gene expression within tumors, leading to improved antigen presentation, T-cell infiltration, and PD-1/PD-L1 expression, ultimately improving the therapeutic outcomes for patients with TNBC.
CLINICAL CANCER RESEARCH
(2021)
Correction
Biochemistry & Molecular Biology
Eva Perez-Guijarro, Howard H. Yang, Romina E. Araya, Rajaa El Meskini, Helen T. Michael, Suman Kumar Vodnala, Kerrie L. Marie, Cari Smith, Sung Chin, Khiem C. Lam, Andres Thorkelsson, Anthony J. Iacovelli, Alan Kulaga, Anyen Fon, Aleksandra M. Michalowski, Willy Hugo, Roger S. Lo, Nicholas P. Restifo, Shyam K. Sharan, Terry Van Dyke, Romina S. Goldszmid, Zoe Weaver Ohler, Maxwell P. Lee, Chi-Ping Day, Glenn Merlino
Article
Oncology
Sebastian Marwitz, Carmen Ballesteros-Merino, Shawn M. Jensen, Martin Reck, Christian Kugler, Sven Perner, Daniel Dromann, Torsten Goldmann, Bernard A. Fox
Summary: The activation of the TGFB pathway in lung cancer patients has been found to negatively impact survival, especially when it comes to the activation of local immune cells affecting disease progression. These findings may help in developing new approaches to treat early-stage lung cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Cell & Tissue Engineering
Keli L. Hippen, Scott N. Furlan, Rahul Roychoudhuri, Ena Wang, Yigang Zhang, Mark J. Osborn, Sarah C. Merkel, Sophia Hani, Margaret L. MacMillan, Frank Cichocki, Jeffrey S. Miller, John E. Wagner, Nicholas P. Restifo, Leslie S. Kean, Bruce R. Blazar
Summary: Human tTregs expanded through repetitive restimulation maintain their Treg gene expression pattern without developing the exhaustion signature of effector T cells. This method of expansion produces Tregs with stable FoxP3 expression and enhanced suppressor function, supporting the possibility of off-the-shelf Treg therapeutics.
Article
Nursing
Jill K. Baird, Shawn M. Jensen, Walter J. Urba, Bernard A. Fox, Jason R. Baird
Summary: The study found that maternal vaccination against SARS-CoV-2 resulted in the presence of protective specific immunoglobulins in human milk that began to significantly increase around 7 days after vaccination, with an IgG-dominant response.
JOURNAL OF HUMAN LACTATION
(2021)
Article
Multidisciplinary Sciences
Fei Mo, Zhiya Yu, Peng Li, Jangsuk Oh, Rosanne Spolski, Liang Zhao, Caleb R. Glassman, Tori N. Yamamoto, Yun Chen, Filip M. Golebiowski, Dalton Hermans, Sonia Majri-Morrison, Lora K. Picton, Wei Liao, Min Ren, Xiaoxuan Zhuang, Suman Mitra, Jian-Xin Lin, Luca Gattinoni, Jonathan D. Powell, Nicholas P. Restifo, K. Christopher Garcia, Warren J. Leonard
Summary: Adoptive transfer of antigen-specific T cells is a significant advancement in cancer immunotherapy, and maintaining a stem-cell-like state before transfer is beneficial for therapeutic efficacy.
Article
Oncology
Janis M. Taube, Kristin Roman, Elizabeth L. Engle, Chichung Wang, Carmen Ballesteros-Merino, Shawn M. Jensen, John McGuire, Mei Jiang, Carla Coltharp, Bethany Remeniuk, Ignacio Wistuba, Darren Locke, Edwin R. Parra, Bernard A. Fox, David L. Rimm, Cliff Hoyt
Summary: This study successfully optimized a highly sensitive and reproducible mIF characterization of the PD-1/PD-L1 axis, demonstrating high concordance across multiple sites for measures of density of specific IC subsets, measures of coexpression, and proximity with single-cell resolution.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Immunology
Rigel J. Kishton, Suman K. Vodnala, Raul Vizcardo, Nicholas P. Restifo
Summary: The administration of T cells as cellular therapy has shown clinical benefit in cancer patients. However, these therapies are not curative for most patients, especially those with solid tumors. Recent research has focused on understanding key factors that regulate the efficacy of T cell therapy and developing strategies to improve clinical outcomes in solid tumors.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Meeting Abstract
Oncology
Robert Saddawi-Konefka, Aoife O'Farrell, Farhoud Faraji, Michael Allevato, Zhiyong Wang, Victoria Wu, Bryan Yung, Nana-Ama Anang, Ida Franiak-Pietryga, Aaron Simon, Shawn Jensen, Bernard Fox, Andrew Sharabi, Ezra Cohen, Joseph Califano, J. Silvio Gutkind
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, Research & Experimental
Haiying Wang, Shih-Ting Tsao, Mingyuan Gu, Chengbing Fu, Feng He, Xiu Li, Mian Zhang, Na Li, Hong-Ming Hu
Summary: In this study, the critical parameters in the CD3(+) T cell isolation process were investigated to improve CAR-T manufacturing. Selecting the appropriate isolation media significantly improved T-cell activation, transduction, and proliferation. Using DPBS as the isolation buffer showed promising results in clinical trials.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Bernard A. Fox, Walter J. Urba, Shawn M. Jensen, David B. Page, Brendan D. Curti, Rachel E. Sanborn, Rom S. Leidner
CLINICAL CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Jeffrey S. Smith, Haley Hanseler, John Welle, Rogan Rattray, Mary Campbell, Tacy Brotherton, Tarsem Moudgil, Thomas F. Pack, Keith Wegmann, Shawn Jensen, Justin Jin, Carlo B. Bifulco, Scott A. Prahl, Bernard A. Fox, Nicholas L. Stucky
Summary: The study tested the feasibility of VHP, UV, and ethanol decontamination on N95 masks, with ethanol and UV showing different degrees of degradation, while VHP treatment showed no significant change. Ethanol treatment was effective in eliminating detectable SARS-CoV-2 RNA in a virucidal experiment.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2021)