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
Tumor CTLA-4 overexpression predicts poor survival in patients with nasopharyngeal carcinoma
Pei Yu Huang,Shan Shan Guo,Yu Zhang,Jia Bin Lu,Qiu Yan Chen,Lin Quan Tang,Lu Zhang,Li Ting Liu,Li Zhang,Hai Qiang Mai +9 more
TL;DR: Cox regression analysis confirmed the prognostic value of tumor CTLA-4 expression, particularly for D-FFS, in NPC patients (p = 0.044), and NPC patients with high tumor CT LA4 expression had a poorer prognosis than those with low expression.
Journal ArticleDOI
Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model
De-Kuan Chang,Eric C. Peterson,Jiusong Sun,Calum Goudie,Ronny Drapkin,Joyce F. Liu,Ursula A. Matulonis,Quan Zhu,Wayne A. Marasco +8 more
TL;DR: MAb2-3 is an agonist antibody that can restore anti-OvCA immunity through modulation of Treg activity through inhibition of IL-2 binding to its receptor.
Journal ArticleDOI
Mycobacterium tuberculosis Promotes Regulatory T-Cell Expansion via Induction of Programmed Death-1 Ligand 1 (PD-L1, CD274) on Dendritic Cells
Jamma Trinath,Jamma Trinath,Mohan S. Maddur,Mohan S. Maddur,Mohan S. Maddur,Srini V. Kaveri,Kithiganahalli Narayanaswamy Balaji,Jagadeesh Bayry +7 more
TL;DR: The results suggest that the Treg expansion observed by Periasamy et al [5] was indeed attributable to modulation of DC (or innate immune cells in general) functions by M. tuberculosis.
Journal ArticleDOI
Anti-PD-1 inhibits Foxp3+ Treg cell conversion and unleashes intratumoural effector T cells thereby enhancing the efficacy of a cancer vaccine in a mouse model
TL;DR: It is demonstrated that high PD-1 expression correlates with increased tumour-infiltrating Treg cells and reduced effector T cells and that when combined with a potent antigen-adjuvant combination, blocking PD- 1 effectively enhances anti-tumour immunity.
Journal ArticleDOI
Immune checkpoint combinations from mouse to man
Midan Ai,Michael A. Curran +1 more
TL;DR: Extending the curative potential of immunotherapy to a larger percentage of patients with a broader spectrum of malignancies will likely require combinations of co-inhibitory blockade and co-stimulatory activation designed to peel back multiple layers of tumor immune suppression while at the same time minimizing immune-mediated toxicity.
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