TNF-α and TGF-β Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus

Ou, Jing Ni; Wiedeman, Alice; Stevens, Anne M.

doi:10.1038/srep00295

Cited by 74 publications

(67 citation statements)

References 56 publications

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“…PD-L1 expression can be modulated by a number of cytokines, including type I and II IFNs, TNFa, and TGFb (16,23,(30)(31)(32). We show that tumor cell expression of PD-L1 can be enhanced following coculture with IFNg and that addition of TNFa can further augment this response.…”

Section: Discussionmentioning

confidence: 83%

Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade

et al. 2014

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Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with aPD-1 or aPD-L1 mAbs generated efficacious CD8 þ T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen-specific memory immune response. Mechanistic investigations showed that IFNg produced by CD8 þ T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti-PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes. Cancer Res; 74(19); 5458-68. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 83%

Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade

et al. 2014

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“…Peripheral blood mononuclear cells and plasma were isolated within 6 h and cryopreserved. PD-L1 expression assays were performed as previously reported (20,35). PD-L1 + cells segregated into monocyte (Mo: CD14 high CD11c + ), activated monocyte (aMo: CD14 + CD11c + CD16 + ), and immature myeloid dendritic cell (mDC: CD14 low CD11c + ) populations.…”

Section: Methodsmentioning

confidence: 99%

Comparison of biomarkers for systemic juvenile idiopathic arthritis

Shenoi

Ni³

et al. 2015

Pediatr Res

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Background: Differentiation of systemic juvenile idiopathic arthritis (SJIA) fever from other childhood fevers is often delayed due to the lack of reliable, specific biomarkers. We hypothesized that PD-L1 expression is dysregulated in SJIA monocytes and compared it to other candidate SJIA biomarkers. Methods: This pilot study enrolled children with fever without source and compared PD-L1 expression on myeloid cells to C-reactive protein, erythrocyte sedimentation rate, leukocyte counts, S100A12, S100A8, S100A9, calprotectin, and procalcitonin. Logistic regression models were fit to test SJIA diagnosis with each marker used as an independent predictor. Receiver operating characteristic curves and area under curve were calculated. Gene expression profiling on a subset of samples was performed. results: Twenty subjects (10 active SJIA, 10 febrile non-SJIA) were enrolled. S100 proteins were significantly elevated in SJIA with >80% sensitivity and >90% specificity. PD-L1 expression was significantly lower in SJIA. Other markers were not specific for SJIA. On exploratory gene analysis, 106 genes were significant for SJIA association, and several of these are associated with immune response pathways. conclusion: In this small cohort, S100 proteins were specific diagnostic biomarkers for SJIA in children with fever. Decreased PD-L1 surface expression on circulating myeloid cells in SJIA suggests possible mechanism for loss of peripheral immune regulation.

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“…Ou et al reported that in SLE monocytes opposing actions of TNF-α and Transforming growth factor (TGF)-β regulated the expression of PD-L1 [74]. PD-L1 expression could be revived by exogenous TNF-α on lupus monocytes [74]. TGF-β has shown to inhibit PD-L1 expression on monocytes [74].…”

Section: Regulation Of Pd-l1mentioning

confidence: 99%

“…Enhanced expression of PD-L1 was present on immature dendritic cells (iDCs) after being treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) [73]. Ou et al reported that in SLE monocytes opposing actions of TNF-α and Transforming growth factor (TGF)-β regulated the expression of PD-L1 [74]. PD-L1 expression could be revived by exogenous TNF-α on lupus monocytes [74].…”

Section: Regulation Of Pd-l1mentioning

confidence: 99%

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The function and regulation of PD-L1 in immunotherapy

Guo¹,

Lin²,

Kwok³

2017

ADMET DMPK

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PD-L1, also known as B7-H1, is a type I transmembrane protein, which is expressed in different kinds of tumor cells. It is correlated with poor clinical outcome of patients with various types of tumors. PD-L1 can regulate tumor microenvironment or tumor related immune response through suppressing T cell or NK cell mediated immune response. PD-L1 expression is regulated by various cytokines, such as LPS, GM-CSF, IL-4, TGF-β, TNF-α. PD-1 and PD-L1 are the members of B7 and CD28 superfamily, respectively. The B7/CD28 interaction plays a central role in immune tolerance. PD-L1 can bind to PD-1, which leads to the suppression of lymphocyte activation and apoptosis of lymphocytes. Anti-PD-L1 therapy is one of the immunotherapies to treat cancer (especially solid tumor). PD-L1 expression may be associated with efficacy

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TNF-α and TGF-β Counter-Regulate PD-L1 Expression on Monocytes in Systemic Lupus Erythematosus

Cited by 74 publications

References 56 publications

Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade

Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade

Comparison of biomarkers for systemic juvenile idiopathic arthritis

The function and regulation of PD-L1 in immunotherapy

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