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Articles 1 - 8 of 8
Full-Text Articles in Medicine and Health Sciences
Meeting Overview: Interferon Lambda - Disease Impact And Therapeutic Potential, Thomas R. O'Brien, Howard A. Young, Raymond P. Donnelly, Ludmila Prokunina-Olsson
Meeting Overview: Interferon Lambda - Disease Impact And Therapeutic Potential, Thomas R. O'Brien, Howard A. Young, Raymond P. Donnelly, Ludmila Prokunina-Olsson
Public Health Resources
A meeting entitled, "Interferon Lambda: Disease Impact and Translational Potential," was held on the campus of the National Institutes of Health in Bethesda, Maryland, on October 25-26, 2018. To our knowledge, this was the first meeting that focused exclusively on interferon lambda (IFN-λ). The meeting's purpose was to enhance interdisciplinary communication and promote new collaborations. The gathering brought together an international group of scientists from a wide range of disciplines. Sessions included: IFN-λ Biology, Therapy and Genetic Variation; IFN-λ and Hepatitis C Virus Infection; IFN-λ in Other Infections; and IFN-λ - Hepatic Fibrosis and Cancer. The next meeting on IFN-λ …
Durvalumab In Combination With Olaparib In Patients With Relapsed Sclc: Results From A Phase Ii Study, Anish Thomas, Rasa Vilimas, Christopher Trindade, Rebecca Erwin-Cohen, Nitin Roper, Liqiang Xi, Venkatesh Krishnasamy, Elliot Levy, Andy Mammen, Samantha Nichols, Yuanbin Chen, Vamsidhar Velcheti, Faye Yin, Eva Szabo, Yves Pommier, Seth M. Steinberg, Jane B. Trepel, Mark Raffeld, Howard A. Young, Javed Khan, Stephen Hewitt, Jung Min Lee
Durvalumab In Combination With Olaparib In Patients With Relapsed Sclc: Results From A Phase Ii Study, Anish Thomas, Rasa Vilimas, Christopher Trindade, Rebecca Erwin-Cohen, Nitin Roper, Liqiang Xi, Venkatesh Krishnasamy, Elliot Levy, Andy Mammen, Samantha Nichols, Yuanbin Chen, Vamsidhar Velcheti, Faye Yin, Eva Szabo, Yves Pommier, Seth M. Steinberg, Jane B. Trepel, Mark Raffeld, Howard A. Young, Javed Khan, Stephen Hewitt, Jung Min Lee
Public Health Resources
Purpose: Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods: A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells …
Ion Gresser 1928-2019, Jan Vilcek, Howard A. Young
Ion Gresser 1928-2019, Jan Vilcek, Howard A. Young
Public Health Resources
Ion Gresser, a virologist who transformed understanding of the roles of interferons, may be best remembered for showing that in mice, interferon-α (IFN-α) can produce acute and chronic disease. At the time Gresser began these studies, interferon was considered to be a selective antiviral substance, harmless to uninfected cells and organisms, and there was no indication that cytokines would play a role in pathogenesis. That belief was shattered with the 1975 Nature publication with the simple title “Lethality of interferon preparations for newborn mice.” Gresser subsequently demonstrated that antibodies to IFN-α can protect young mice from death caused by infection …
Ifn-Γ: A Cytokine At The Right Time, Is In The Right Place, J. Daniel Burke, Howard A. Young
Ifn-Γ: A Cytokine At The Right Time, Is In The Right Place, J. Daniel Burke, Howard A. Young
Public Health Resources
Interferon gamma has long been studied as a critical mediator of tumor immunity. In recent years, the complexity of cellular interactions that take place in the tumor microenvironment has become better appreciated in the context of immunotherapy. While checkpoint inhibitors have dramatically improved remission rates in cancer treatment, IFN-Γ and related effectors continue to be identified as strong predictors of treatment success. In this review, we provide an overview of the multiple immunosuppressive barriers that IFN-Γ has to overcome to eliminate tumors, and potential avenues for modulating the immune response in favor of tumor rejection.
Report On The 2018 Cancer, Autoimmunity, And Immunology Conference, Colleen S. Curran, Connie L. Sommers, Howard A. Young, Katarzyna Bourcier, Marie Mancini, Elad Sharon
Report On The 2018 Cancer, Autoimmunity, And Immunology Conference, Colleen S. Curran, Connie L. Sommers, Howard A. Young, Katarzyna Bourcier, Marie Mancini, Elad Sharon
Public Health Resources
With the increased use of cancer immunotherapy, a number of immune-related adverse events (irAEs) are being identified. These irAEs can be compared with known autoimmune disorders in similar tissues, with important similarities and differences. Understanding the etiology of irAEs may bring to light concepts applicable to immune responses in cancer, autoimmunity, and infectious disease. This immunobiology is especially relevant to cancer patients with preexisting allogeneic transplants or autoimmune disease who are undergoing cancer immunotherapy. To address these facets of cancer immunotherapy, academic leaders from these various disciplines discussed current irAE basic and clinical research, irAE diagnosis and management, and the …
Critical Role Of Post-Transcriptional Regulation For Ifn-Γ In Tumor-Infiltrating T Cells, Fiamma Salerno, Aurelie Guislain, Julian J. Freen-Van Heeren, Benoit P. Nicolet, Howard A. Young, Monika C. Wolkers
Critical Role Of Post-Transcriptional Regulation For Ifn-Γ In Tumor-Infiltrating T Cells, Fiamma Salerno, Aurelie Guislain, Julian J. Freen-Van Heeren, Benoit P. Nicolet, Howard A. Young, Monika C. Wolkers
Public Health Resources
Protective T cell responses against tumors require the production of Interferon gamma (IFN-γ). However, tumor-infiltrating T cells (TILs) gradually lose their capacity to produce IFN-γ and therefore fail to clear malignant cells. Dissecting the underlying mechanisms that block cytokine production is thus key for improving T cell products. Here we show that although TILs express substantial levels of Ifng mRNA, post-transcriptional mechanisms impede the production of IFN-γ protein due to loss of mRNA stability. CD28 triggering, but not PD1 blocking antibodies, effectively restores the stability of Ifng mRNA. Intriguingly, TILs devoid of AU-rich elements within the 3ʹuntranslated region maintain stabilized …
Partners In Crime: Fledgling Tumors Hijack Inflammation, Balamurugan Kuppusamy, Howard A. Young
Partners In Crime: Fledgling Tumors Hijack Inflammation, Balamurugan Kuppusamy, Howard A. Young
Public Health Resources
While inflammation is a normal physiological response after tissue injury, the chemicals/mediators that are released by the damaged tissue can be toxic to the cells. This underlying inflammation increases the likelihood of cellular DNA damage and aberrant cell growth (Kiraly and others 2015). In this scenario, inflammation functions as a ‘‘behind-curtain factor’’ for many disorders. Cancer has long been known to be closely tethered to inflammation. Widespread evidence shows that inflammatory diseases such as colitis, pancreatitis, and hepatitis make their respective organs highly susceptible to eventual cancer development (Shalapour and Karin 2015). However, other studies have shown that in due …
Thymic Expression Of Il-4 And Il-15 After Systemic Inflammatory Or Infectious Th1 Disease Processes Induce The Acquisition Of"Innate" Characteristics During Cd8 + T Cell Development, Natalia S. Baez, Fabio Cerbán, Constanza Savid-Frontera, Deborah L. Hodge, Jimena Tosello, Eva Acosta-Rodriguez, Laura Almada, Adriana Gruppi, Maria Estefania Viano, Howard A. Young, Maria Cecilia Rodriguez-Galan
Thymic Expression Of Il-4 And Il-15 After Systemic Inflammatory Or Infectious Th1 Disease Processes Induce The Acquisition Of"Innate" Characteristics During Cd8 + T Cell Development, Natalia S. Baez, Fabio Cerbán, Constanza Savid-Frontera, Deborah L. Hodge, Jimena Tosello, Eva Acosta-Rodriguez, Laura Almada, Adriana Gruppi, Maria Estefania Viano, Howard A. Young, Maria Cecilia Rodriguez-Galan
Public Health Resources
Innate CD8 + T cells express a memory-like phenotype and demonstrate a strong cytotoxic capacity that is critical during the early phase of the host response to certain bacterial and viral infections. These cells arise in the thymus and depend on IL-4 and IL-15 for their development. Even though innate CD8 + T cells exist in the thymus of WT mice in low numbers, they are highly enriched in KO mice that lack certain kinases, leading to an increase in IL-4 production by thymic NKT cells. Our work describes that in C57BL/6 WT mice undergoing a Th1 biased infectious disease, …