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-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1
Shigeki Chiba,Muhammad Baghdadi,Hisaya Akiba,Hironori Yoshiyama,Ichiro Kinoshita,Hirotoshi Dosaka-Akita,Yoichiro Fujioka,Yusuke Ohba,Jacob V. Gorman,John D. Colgan,Mitsuomi Hirashima,Toshimitsu Uede,Akinori Takaoka,Hideo Yagita,Masahisa Jinushi +14 more
TL;DR: Tumor-associated dendritic cells in mouse tumors and patients with cancer had high expression of TIM-3, which suppressed innate immune responses through the recognition of nucleic acids by Toll-like receptors and cytosolic sensors via a galectin-9-independent mechanism.
Journal Article
Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity.
Osamu Nakano,Makoto Sato,Yoshitaka Naito,Kenichi Suzuki,Seiichi Orikasa,Masataka Aizawa,Yasuyoshi Suzuki,Ichirou Shintaku,Hiroshi Nagura,Haruo Ohtani +9 more
TL;DR: The data in human renal cell carcinoma suggest that infiltration of tumor tissue by T cells itself does not denote the efficacy of antitumor immunity because of its dependence on the biological malignancy of tumor cells, but infiltration of tumors by CD8(+) T cells bearing more pronounced proliferative activity could reflect effective antitumors immunity.
Journal ArticleDOI
Reversal of the TCR stop signal by CTLA-4.
Helga Schneider,Helga Schneider,Jos Downey,Andrew M. Smith,Bernd H. Zinselmeyer,Bernd H. Zinselmeyer,Catherine M. Rush,Catherine M. Rush,James M. Brewer,James M. Brewer,Bin Wei,Nancy Hogg,Paul Garside,Paul Garside,Christopher E. Rudd,Christopher E. Rudd +15 more
TL;DR: It is shown that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)–induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells, which suggests a fundamentally different model of reverse stop signaling.
Journal ArticleDOI
Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells.
TL;DR: Results show that regulatory T cells are the major regulators of concomitant tumor immunity against this weakly immunogenic tumor.
Journal ArticleDOI
Regulatory T cells in cancer immunotherapy.
TL;DR: In this paper, an optimal strategy was established for reducing Treg cells or attenuating their suppressive activity in tumor tissues, together with activating and expanding tumor-specific effector T cells.
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