Journal ArticleDOI
Immune checkpoints and their inhibition in cancer and infectious diseases.
Lydia Dyck,Kingston H. G. Mills +1 more
TLDR
These inhibitors have great potential for treating chronic infections, especially when combined with therapeutic vaccines, and have been shown to enhance ex vivo effector T‐cell responses from patients with chronic viral, bacterial, or parasitic infection.Abstract:
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion. Given their role in suppressing effector T-cell responses, immune checkpoints are being targeted for the treatment of cancer. Indeed, antibodies binding to CTLA-4, PD-1, or PD-L1 have shown remarkable efficacy, especially in combination therapies, for a number of cancers and have been licensed for the treatment of melanoma, nonsmall cell lung cancer, and renal and bladder cancers. Moreover, immune checkpoint inhibitors have been shown to enhance ex vivo effector T-cell responses from patients with chronic viral, bacterial, or parasitic infection, including HIV, tuberculosis, and malaria. Although the data from clinical trials in infectious diseases are still sparse, these inhibitors have great potential for treating chronic infections, especially when combined with therapeutic vaccines.read more
Citations
More filters
Journal ArticleDOI
Advances in the understanding and treatment of sepsis-induced immunosuppression
TL;DR: The reappraisal of sepsis pathophysiology has resulted in a novel approach to the design of clinical trials evaluating sepsi treatments, based on an evaluation of the immune status and biomarker-based stratification of patients.
Journal ArticleDOI
Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment
Xingzhe Ma,Enguang Bi,Yong Lu,Pan Su,Chunjian Huang,Lintao Liu,Qiang Wang,Maojie Yang,Matthew F. Kalady,Jianfei Qian,Aijun Zhang,Anisha A. Gupte,Dale J. Hamilton,Chengyun Zheng,Qing Yi +14 more
TL;DR: It is reported that cholesterol in the tumor microenvironment induces CD8+ T cell expression of immune checkpoints and exhaustion and a new strategy for restoring T-cell function by reducing cholesterol to enhance T cell-based immunotherapy is suggested.
Journal ArticleDOI
Clinical update on head and neck cancer: molecular biology and ongoing challenges.
E. Alsahafi,Katheryn Begg,Ivano Amelio,Nina Raulf,Philippe Lucarelli,Thomas Sauter,Mahvash Tavassoli +6 more
TL;DR: This update aims to build on the earlier 2014 review by bringing up to date the understanding of the molecular biology of HNSCCs and provide insights into areas of ongoing research and perspectives for the future.
Journal ArticleDOI
Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies
Simon Tiberi,Nelita du Plessis,Gerhard Walzl,Michael J. Vjecha,Martin Rao,Francine Ntoumi,Sayoki Mfinanga,Nathan Kapata,Peter Mwaba,Timothy D. McHugh,Giuseppe Ippolito,Giovanni Battista Migliori,Markus Maeurer,Alimuddin Zumla +13 more
TL;DR: The developmental pipeline and landscape of new and repurposed tuberculosis drugs, treatment regimens, and host-directed therapies (HDTs) for drug-sensitive and drug-resistant tuberculosis are reviewed and a range of HDTs and immune-based treatments are under investigation as adjunctive therapy.
Journal ArticleDOI
Current progress in innovative engineered antibodies.
TL;DR: There are currently at least 864 antibody- based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.
References
More filters
PD-1 modulates steady-state and infection-induced IL-10 production in vivo - eScholarship
Debroski Herbert,Cortez McBerry,Alexandra Dias,Nathaniel Shryock,Kristin Lampe,Frs Gutierrez,Louis Boon,Herbert,Julio Aliberti +8 more
TL;DR: The results demonstrate that PD‐1‐deficient mice have increased susceptibility to T. gondii, with increased parasite cyst counts along with reduced type‐1 cytokine responses (IL‐12 and IFN‐γ) and show that IL‐10 suppresses the development of protective Th1 immune response after T. Gondii infection.
Journal ArticleDOI
Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumor immunity
TL;DR: The findings demonstrate that pathogen-associated molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory T cells, and that the environment of the growing tumor influences the protective effect.
Related Papers (5)
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.
James Larkin,Vanna Chiarion-Sileni,Rene Gonzalez,Jean-Jacques Grob,C. Lance Cowey,Christopher D. Lao,Dirk Schadendorf,Reinhard Dummer,Michael Smylie,Piotr Rutkowski,Pier Francesco Ferrucci,A. Hill,John Wagstaff,Matteo S. Carlino,John B A G Haanen,Michele Maio,Ivan Marquez-Rodas,Grant A. McArthur,Paolo A. Ascierto,Georgina V. Long,Margaret K. Callahan,Michael A. Postow,Michael A. Postow,Kenneth F. Grossmann,Mario Sznol,Brigitte Dréno,Lars Bastholt,Arvin Yang,Linda Rollin,Christine Horak,F. Stephen Hodi,Jedd D. Wolchok,Jedd D. Wolchok +32 more
Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer
Hossein Borghaei,Luis Paz-Ares,Leora Horn,D. R. Spigel,M. Steins,Neal Ready,L.Q. Chow,Everett E. Vokes,Enriqueta Felip,Esther Holgado,F. Barlesi,M. Kohlhufl,Oscar Arrieta,Marco Angelo Burgio,J. Fayette,H. Lena,Elena Poddubskaya,David E. Gerber,Scott N. Gettinger,Charles M. Rudin,Naiyer A. Rizvi,L. Crina,G. R. Blumenschein,Scott J. Antonia,C. Dorange,C. T. Harbison,F. Graf Finckenstein,Julie R. Brahmer +27 more