Immune checkpoints and their inhibition in cancer and infectious diseases

Dyck, Lydia; Mills, Kingston H. G.

doi:10.1002/eji.201646875

Cited by 443 publications

(431 citation statements)

References 167 publications

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“…Immune regulatory checkpoints are perturbed in TB and linked to T-cell exhaustion. 115 Signalling via immune checkpoints inhibit T-and B-cell function 116 . Checkpoint inhibitors have been successfully employed in various cancers, specifically the monoclonal antibodies nivolumab and ipilimumab, against PD-1 and CTLA-4, respectively.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

306

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

306

275

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“…Interaction of programed death 1 (PD-1) with its ligand such as PD-L1 or PD-L2 delivers an inhibitory signal to T cells that affects cell proliferation and cytokine production [161]. HIV infection enhances the expressions of PD-1 in T cells and PD-L1 and PD-L2 in macrophages [161,162,163,164]. PD-1 engagement with its ligands has been described to play a role in T cell exhaustion as a result of chronic HIV infection [162,165,166].…”

Section: Cav-1 Mediated Hiv Inhibitionmentioning

confidence: 99%

The Role of Caveolin 1 in HIV Infection and Pathogenesis

Mergia

2017

Viruses

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Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.

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“…Tumor PI may also act as an immunomodulatory mechanism influencing immunotherapy of cancer, either negatively or positively. For example, PD-1 ligand (PD-L1) expression is indicative of the success of anti-PD1 treatment [32]. We found that PD-L1 gene expression is strongly linked to PI: PD-L1 is induced in PI+ mouse APC −/− adenomas, and attenuated in response to Sulindac (Aran et al, unpublished); PD-L1 is also expressed in the majority of PI+ samples in both carcinoma cell lines and primary tumors.…”

Section: Future Directionsmentioning

confidence: 99%

Cancer Cell–Autonomous Parainflammation Mimics Immune Cell Infiltration

et al. 2017

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Parainflammation is a unique variant of inflammation, characterized by epithelial-autonomous activation of inflammatory response. Parainflammation has been shown to strongly promote mouse gut tumorigenesis upon p53 loss. In a recent study, we explored the prevalence of parainflammation in human cancer and determined its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Parainflammation can be identified from a 40-gene signature, and is found in both carcinoma cell lines and a variety of primary tumors, independently of tumor microenvironment. Here we discuss the implications of our findings in analyses of tumor microenvironment, suggesting that as tumor cell gene expression may often mimic immune and inflammatory infiltration, caution should be applied when interpreting tumor expression data. We also address the connection between parainflammation and prevalence of p53 mutations in specific types of tumors, and cancer prevention by regular usage of NSAIDs. We suggest that parainflammation may serve as a novel biomarker for screening patients who may particularly benefit from NSAID treatment.

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Immune checkpoints and their inhibition in cancer and infectious diseases

Cited by 443 publications

References 167 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

The Role of Caveolin 1 in HIV Infection and Pathogenesis

Cancer Cell–Autonomous Parainflammation Mimics Immune Cell Infiltration

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