Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

Mallett, Grace; Laurence, Arian; Amarnath, Shoba

doi:10.3390/ijms20112836

Cited by 24 publications

(22 citation statements)

References 74 publications

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“…For instance, in effector T cells expressing PD-1, PD-L1 binding suppresses TCR or costimulatory signaling, resulting in T-cell apoptosis, anergy, and exhaustion (2, 43–46). In innate lymphoid cells (ILC2s), PD-L1 binding to the PD-1 receptor dampens ILC2 proliferation and function (47). However, PD-L1 binding to PD-1 on regulatory T (Treg) cells leads to their proliferation.…”

Section: Pd-1/pd-l Axis Functionmentioning

confidence: 99%

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

et al. 2019

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The recent success of PD-1 and PD-L1 blockade in cancer therapy illustrates the important role of the PD-1/PD-L1 pathway in the regulation of antitumor immune responses. However, signaling regulated by the PD-1/PD-L pathway is also associated with substantial inflammatory effects that can resemble those in autoimmune responses, chronic infection, and sepsis, consistent with the role of this pathway in balancing protective immunity and immunopathology, as well as in homeostasis and tolerance. Targeting PD-1/PD-L1 to treat cancer has shown benefits in many patients, suggesting a promising opportunity to target this pathway in autoimmune and inflammatory disorders. Here, we systematically evaluate the diverse biological functions of the PD-1/PD-L pathway in immune-mediated diseases and the relevant mechanisms that control these immune reactions.

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Section: Pd-1/pd-l Axis Functionmentioning

confidence: 99%

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

et al. 2019

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“…In addition to analyzing the influence of loading the T cells with SPION Citrate on the release of IL-2, the expression of different activation markers was also investigated. Cell surface staining for the activation markers CD25 and CD69 as well as the checkpoint molecules programmed cell death 1 (PD-1, CD279), lymphocyte activation gene 3 (LAG-3, CD223), and T cell immunoglobulin and mucin domain containing 3 (Tim-3, CD366) were analyzed by flow cytometry [56][57][58][59][60][61][62][63][64]. After exclusion of doublets and higher cell aggregates, dead cells were excluded by DAPI staining and only DAPI − cells were evaluated [65].…”

Section: Effects Of Spion Citrate On T Cell Activationmentioning

confidence: 99%

Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation

Mühlberger

Unterweger

Band

et al. 2020

Cells

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For the conversion of immunologically cold tumors, characterized by a low T cell infiltration, into hot tumors, it is necessary to enrich T cells in the tumor area. One possibility is the use of magnetic fields to direct T cells into the tumor. For this purpose, primary T cells that were freshly isolated from human whole blood were loaded with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONCitrate). Cell toxicity and particle uptake were investigated by flow cytometry and atomic emission spectroscopy. The optimum loading of the T cells without any major effect on their viability was achieved with a particle concentration of 75 µg Fe/mL and a loading period of 24 h. The cellular content of SPIONCitrate was sufficient to attract these T cells with a magnet which was monitored by live-cell imaging. The functionality of the T cells was only slightly influenced by SPIONCitrate, as demonstrated by in vitro stimulation assays. The proliferation rate as well as the expression of co-stimulatory and inhibitory surface molecules (programmed cell death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain containing 3 (Tim-3), C-C motif chemokine receptor 7 (CCR7), CD25, CD45RO, CD69) was investigated and found to be unchanged. Our results presented here demonstrate the feasibility of loading primary human T lymphocytes with superparamagnetic iron oxide nanoparticles without influencing their viability and functionality while achieving sufficient magnetizability for magnetically controlled targeting. Thus, the results provide a strong fundament for the transfer to tumor models and ultimately for new immunotherapeutic approaches for cancer treatment.

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“…PD-L1 is primarily expressed in inflamed tissues and tumors. Thus, PD-L1 expression in the tumor microenvironment will reduce the T cell-based antitumor immune response [10,23,24]. Two anti-PD-1 monoclonal antibodies (nivolumab and pembrolizumab) [25][26][27] and three anti-PD-L1 monoclonal antibodies (atezolizumab, avelumab, and durvalumab) [28][29][30] have been approved by the US Food and Drug Administration (FDA) for treating cancers, for example, melanoma, nonsmall cell lung cancer, and renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target

Farschtschi

Park

et al. 2020

Cancer Immunol Immunother

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Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare aggressive sarcomas with poor prognosis. More than half of MPNSTs develop from benign precursor tumors associated with neurofibromatosis type 1 (NF1) which is a tumor suppressor gene disorder. Early detection of malignant transformation in NF1 patients is pivotal to improving survival. The primary aim of this study was to evaluate the role of immuno-modulators as candidate biomarkers of malignant transformation in NF1 patients with plexiform neurofibromas as well as predictors of response to immunotherapeutic approaches. Methods Sera from a total of 125 NF1 patients with quantified internal tumor load were included, and 25 of them had MPNSTs. A total of six immuno-modulatory factors (IGFBP-1, PD-L1, IFN-α, GM-CSF, PGE-2, and AXL) were measured in these sera using respective ELISA. Results NF1 patients with MPNSTs had significantly elevated PD-L1 levels in their sera compared to NF1 patients without MPNSTs. By contrast, AXL concentrations were significantly lower in sera of NF1-MPNST patients. IGFBP-1 and PGE2 serum levels did not differ between the two patient groups. IFN-α and GM-CSF were below the detectable level in most samples. Conclusion The immuno-modulator PD-L1 is upregulated in MPNST patients and therefore may provide as a potential biomarker of malignant transformation in patients with NF1 and as a response predictor for immunotherapeutic approaches.

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Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells

Cited by 24 publications

References 74 publications

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

The Diverse Function of PD-1/PD-L Pathway Beyond Cancer

Loading of Primary Human T Lymphocytes with Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Does Not Impair Their Activation after Polyclonal Stimulation

Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target

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