Inborn Errors of Immunity and Their Phenocopies: CTLA4 and PD-1

Hao, Yuwei; Cook, Matthew

doi:10.3389/fimmu.2021.806043

Cited by 10 publications

(6 citation statements)

References 133 publications

(162 reference statements)

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“…To overcome resistance to single-agent immunotherapy, combinations of agents targeting different immune modulators has been tested. Combination therapies with two checkpoint inhibitor antibodies, anti-PD-1 and anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA4), have resulted in an increased response rate 55,56 ; however, severe immune-associated adverse events have also been reported 57 . Agonist antibodies against OX40 with ICBs are being tested against various types of cancers in early-phase clinical trials 17 .…”

Section: Discussionmentioning

confidence: 99%

OX40 expressed in endothelial cells facilitates tumor cells to escape from T-cell surveillance through S1P-YAP axis

Zhang,

He,

Zhao

et al. 2024

Preprint

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Activation of immune cells is currently one of the most promising approaches for the cancer treatment. However, clinical trials for T-cell activation therapy have not reached expected results without explicit reasons. In the present study, we report that the co-stimulatory molecule OX40 is highly expressed in endothelial cells (ECs) of tumor tissues. Clinically, high expression of OX40 in ECs is negatively associated with the prognosis of tumor patients, and this is irrelevant to T-cell activation or not. Analysis of conditional OX40 loss- and gain-of-function transgenic mice demonstrated that OX40 signals promote angiogenesis and facilitate the tumour development. Mechanistically, Lgr5+ cancer stem cells induced high OX40 expression in tumour ECs via EGF-STAT3 signal transduction. In ECs, activated OX40 interacted with Spns2, obstructing sphingosine-1-phosphate (S1P) export and resulting in its intracellular accumulation. S1P directly bound to YAP, disrupting its interaction with the LATS1 kinase and promoting YAP nuclear translocation. Finally, the YAP inhibitor Verteporfin enhanced the anti-tumour effects of the OX40 agonist. In addition, their combination exhibited greater efficacy than that of the OX40 agonist and anti-PD-1 antibody. Together, the findings revealed a unexpected pro-tumour functions of OX40 activation in ECs, highlighting the impact of non-immune cell compartment on immunotherapy and the complexity of tumour microenvironment.

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Section: Discussionmentioning

confidence: 99%

OX40 expressed in endothelial cells facilitates tumor cells to escape from T-cell surveillance through S1P-YAP axis

Zhang,

He,

Zhao

et al. 2024

Preprint

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“…For example, CTLA-4 deficiency in humans can be associated with pathologies in several organs, such as the lungs, gastrointestinal tract, brain, bone marrow, kidney, and retroperitoneal tissue. 163 …”

Section: Discussionmentioning

confidence: 99%

Distinct T helper cell-mediated antitumor immunity: T helper 2 cells in focus

Silva¹,

Lopes²,

Correa³

2023

Cancer Pathogenesis and Therapy

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“…Autoimmune lymphoproliferative syndrome due to CTLA-4 haploinsufficiency is a rare genetic immunodeficiency characterized by mutations in a key immune regulatory protein. Clinical features of the disease include hypogammaglobulinemia, lymphoproliferation, autoimmune cytopenias as well as gastrointestinal and respiratory manifestations [41]. A notable respiratory manifestation is GLILD.…”

Section: Interstitial Lung Disease In Other Predominantly Antibody De...mentioning

confidence: 99%

Interstitial lung diseases in inborn errors of immunity

Sullivan,

Maniam,

Maglione

2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Our goal is to review current understanding of interstitial lung disease (ILD) affecting patients with inborn errors of immunity (IEI). This includes understanding how IEI might predispose to and promote development or progression of ILD as well as how our growing understanding of IEI can help shape treatment of ILD in these patients. Additionally, by examining current knowledge of ILD in IEI, we hope to identify key knowledge gaps that can become focus of future investigative efforts. Recent findings Recent identification of novel IEI associated with ILD and the latest reports examining treatment of ILD in IEI are included. Of noted interest, are recent clinical studies of immunomodulatory therapy for ILD in common variable immunodeficiency. Summary ILD is a frequent complication found in many IEI. This article provides a guide to identifying manifestations of ILD in IEI. We review a broad spectrum of IEI that develop ILD, including antibody deficiency and immune dysregulation disorders that promote autoimmunity and autoinflammation. This work integrates clinical information with molecular mechanisms of disease and diagnostic assessments to provide an expedient overview of a clinically relevant and expanding topic.

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Inborn Errors of Immunity and Their Phenocopies: CTLA4 and PD-1

Cited by 10 publications

References 133 publications

OX40 expressed in endothelial cells facilitates tumor cells to escape from T-cell surveillance through S1P-YAP axis

OX40 expressed in endothelial cells facilitates tumor cells to escape from T-cell surveillance through S1P-YAP axis

Distinct T helper cell-mediated antitumor immunity: T helper 2 cells in focus

Interstitial lung diseases in inborn errors of immunity

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