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
Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study
Minoru Miyashita,Hironobu Sasano,Kentaro Tamaki,Hisashi Hirakawa,Yayoi Takahashi,Saki Nakagawa,Gou Watanabe,Hiroshi Tada,Akihiko Suzuki,Noriaki Ohuchi,Takanori Ishida +10 more
TL;DR: This is the first study to demonstrate that high CD8+ TIL and a highCD8/FOXP3 ratio in residual tumors and increment of these parameters following NAC and accurately predict improved prognosis in TNBC patients with non-pathological complete response following Nac.
Journal ArticleDOI
Targeting regulatory T cells in tumors
TL;DR: It is proposed that discovering and understanding mechanisms that are preferentially used by Treg cells within the tumor microenvironment will lead to strategies that selectively target Treg cell‐mediated suppression of antitumor immunity while maintaining peripheral immune tolerance.
Journal ArticleDOI
PD-1 Blockade Boosts Radiofrequency Ablation–Elicited Adaptive Immune Responses against Tumor
Liangrong Shi,Lujun Chen,Changping Wu,Yibei Zhu,Bin Xu,Xiao Zheng,Mingfen Sun,Wen Wen,Xichao Dai,Min Yang,Quansheng Lv,Binfeng Lu,Jingting Jiang +12 more
TL;DR: The PD-L1–PD-1 axis plays a critical role in dampening RFA-induced antitumor immune responses, and this study provides a strong rationale for combining RFA and the PD- L1/ PD-1 blockade in the clinical setting.
Journal ArticleDOI
PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment.
Jing Li,Hyun-Bae Jie,Yu Lei,Neil Gildener-Leapman,Sumita Trivedi,Tony Green,Lawrence P. Kane,Robert L. Ferris +7 more
TL;DR: It is argued that PD-1 or SHP-2 blockade will be sufficient to restore robust Th1 immunity and T-cell activation and thereby reverse immunosuppression in the tumor microenvironment.
Journal ArticleDOI
Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection
Soumita Das,Giovanni Suarez,Ellen J. Beswick,Johanna C. Sierra,David Y. Graham,Victor E. Reyes +5 more
TL;DR: A role for B7-H1 on the epithelium as a contributor in the chronicity of H. pylori infection is suggested, involved in the suppression of T cell proliferation and IL-2 synthesis.
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