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
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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
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Journal ArticleDOI
PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines
Weiyi Peng,Chengwen Liu,Chunyu Xu,Yanyan Lou,Jieqing Chen,Yan Yang,Hideo Yagita,Willem W. Overwijk,Gregory Lizée,Laszlo Radvanyi,Patrick Hwu +10 more
TL;DR: Results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites.
Journal ArticleDOI
CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer
Shuzhen Liu,Jonathan Lachapelle,Samuel Leung,Dongxia Gao,William D. Foulkes,William D. Foulkes,William D. Foulkes,Torsten O. Nielsen +7 more
TL;DR: The presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival.
Journal ArticleDOI
Orchestration and Prognostic Significance of Immune Checkpoints in the Microenvironment of Primary and Metastatic Renal Cell Cancer
Nicolas A. Giraldo,Nicolas A. Giraldo,Nicolas A. Giraldo,Etienne Becht,Etienne Becht,Etienne Becht,Franck Pagès,Georgios P Skliris,Virginie Verkarre,Yann Vano,Arnaud Mejean,Nicolas Saint-Aubert,Laetitia Lacroix,Laetitia Lacroix,Laetitia Lacroix,Ivo Natario,Ivo Natario,Ivo Natario,Audrey Lupo,Marco Alifano,Diane Damotte,Aurélie Cazes,Frédéric Triebel,Gordon J. Freeman,Marie-Caroline Dieu-Nosjean,Marie-Caroline Dieu-Nosjean,Marie-Caroline Dieu-Nosjean,Stéphane Oudard,Wolf H. Fridman,Catherine Sautès-Fridman +29 more
TL;DR: The expression of the immune checkpoints and the localization of DC in the tumor microenvironment modulate the clinical impact of CD8+ T cells in ccRCC.
Journal ArticleDOI
HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade
David M. Woods,Andressa L. Sodre,Alejandro Villagra,Amod A. Sarnaik,Eduardo M. Sotomayor,Jeffrey S. Weber +5 more
TL;DR: It is shown that class I HDAC inhibitor treatment resulted in rapid upregulation of histone acetylation of the PD-L1 gene leading to enhanced and durable gene expression, providing a rationale for combining HDAC inhibitors with PD-1 blockade.
Journal ArticleDOI
CD4/major histocompatibility complex class II interaction analyzed with CD4‐ and lymphocyte activation gene‐3 (LAG‐3)‐Ig fusion proteins
TL;DR: Results suggest that co‐engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG‐3Ig competition.
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