Interferon‐induced programmed death‐ligand 1 (<scp>PD</scp>‐<scp>L</scp>1/<scp>B</scp>7‐<scp>H</scp>1) expression increases on human acute myeloid leukemia blast cells during treatment

Krönig, Holger; Kremmler, Lukas; Haller, Bernhard; Englert, Carsten; Peschel, Christian; Andreesen, Reinhard; Blank, Christian U.

doi:10.1111/ejh.12228

Cited by 94 publications

(78 citation statements)

References 46 publications

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“…Nevertheless, the existing data suggest that activity of the PD-1/PD-L1 pathway, similar to Treg-mediated suppression, 70 may be particularly increased upon recovery from cytotoxic chemotherapy. 76 Consistent with these observations, PD-L1 expression in CD34+ cells prior to treatment did not appear to have prognostic significance in small cohorts of patients with AML. In 72 patients with MDS or AML tested prior to any treatment, PD-L1 expression in CD34+ cells was not associated with worse survival.…”

Section: Pd-1 Pathway In Acute Myeloid Leukemiasupporting

confidence: 54%

“…However, stimulation with IFN-γ significantly increased PD-L1 expression on AML blasts but not in normal controls. 76 Interestingly, PD-L1 expression on myeloid precursor cells increased more dramatically with IFN-γ stimulation in samples of patients in complete remission or at relapse than in myeloid precursor cells of newly-diagnosed AML patients. 76 These findings demonstrate that PD-L1 expression on myeloid precursor cells and leukemic blasts occurs in a substantial portion of patients with AML.…”

Section: Pd-1 Pathway In Acute Myeloid Leukemiamentioning

confidence: 93%

“…76 Interestingly, PD-L1 expression on myeloid precursor cells increased more dramatically with IFN-γ stimulation in samples of patients in complete remission or at relapse than in myeloid precursor cells of newly-diagnosed AML patients. 76 These findings demonstrate that PD-L1 expression on myeloid precursor cells and leukemic blasts occurs in a substantial portion of patients with AML. At this time, it is not clear whether the frequency of positive cells or levels of expression can be related to disease progression or relapse.…”

Section: Pd-1 Pathway In Acute Myeloid Leukemiamentioning

confidence: 93%

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Programmed death-1 checkpoint blockade in acute myeloid leukemia

Sehgal

Whiteside

Boyiadzis

2015

Expert Opinion on Biological Therapy

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Introduction Immune checkpoints are regulatory pathways induced in activated T lymphocytes that regulate antigen responsiveness. These immune checkpoints are hijacked by tumors to promote dysfunction of anti-tumor effector cells and consequently of tumor escape from the host immune system. Areas covered PD1/PDL-1, a checkpoint pathway, has been extensively investigated in leukemia mouse models. Expression of PD-1 on the surface of activated immune cells and of its ligands, PD-L1 and PD-L2, on leukemic blasts has been documented. Clinical trials with PD-1 inhibitors in patients with hematological malignancies are ongoing with promising clinical responses. Expert Opinion Therapy of hematological cancers with antibodies blocking inhibitory receptors is expected to be highly clinically effective. Checkpoint inhibitory receptors and their ligands are co-expressed on hematopoietic cells found in the leukemic milieu. Several distinct immunological mechanisms are likely to be engaged by antibody-based checkpoint blockade. Co-expression of multiple inhibitory receptors on hematopoietic cells offers an opportunity for combining blocking antibodies to achieve more effective therapy. Up-regulation of receptor/ligand expression in the leukemic milieu may provide a blood marker predictive of response. Finally, chemotherapy-induced up-regulation of PD-1 on T cells after conventional leukemia therapy creates a solid rationale for application of checkpoint blockade as a follow-up therapy.

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Section: Pd-1 Pathway In Acute Myeloid Leukemiasupporting

confidence: 54%

Section: Pd-1 Pathway In Acute Myeloid Leukemiamentioning

confidence: 93%

Section: Pd-1 Pathway In Acute Myeloid Leukemiamentioning

confidence: 93%

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Programmed death-1 checkpoint blockade in acute myeloid leukemia

Sehgal

Whiteside

Boyiadzis

2015

Expert Opinion on Biological Therapy

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“…By contrast, the injection of IFN-γ into subcutaneous tumors increased PD-L1 expression and promoted tumor growth [68]. Moreover, IFN-γ or toll-like receptor (TLR) stimulation upregulated PD-L1 expression in blast cells from patients with acute myeloid leukemia through MEK/ERK- and MyD88/TRAF6 pathway [69]. Chen et al demonstrated that protein kinase D isoform 2 (PKD2), which is induced by IFN-γ, is an important regulator of PD-L1 expression in human oral squamous carcinoma cells.…”

Section: Pd-1 Ligands and The Regulation Of Their Expressionmentioning

confidence: 99%

“…Chen et al demonstrated that protein kinase D isoform 2 (PKD2), which is induced by IFN-γ, is an important regulator of PD-L1 expression in human oral squamous carcinoma cells. Inhibition of PKD2 activation not only suppresses PD-L1 expression and enhances an anti-tumor effect but also reduces drug resistance during chemotherapy [69]. By contrast, natural killer (NK) cell activation and secretion of IFN-γ significantly enhanced PD-L1 expression by activating JAK1, JAK2, and STAT1 in tumor cells.…”

Section: Pd-1 Ligands and The Regulation Of Their Expressionmentioning

confidence: 99%

PD-1 and its ligands are important immune checkpoints in cancer

2016

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Checkpoint programmed death-1 (PD-1)/programmed cell death ligands (PD-Ls) have been identified as negative immunoregulatory molecules that promote immune evasion of tumor cells. The interaction of PD-1 and PD-Ls inhibits the function of T cells and tumor-infiltrating lymphocytes (TIL) while increasing the function of immunosuppressive regulatory T cells (Tregs). This condition causes the tumor cells to evade immune response. Thus, the blockade of PD-1/PD-L1 enhances anti-tumor immunity by reducing the number and/or the suppressive activity of Tregs and by restoring the activity of effector T cells. Furthermore, some monoclonal antibodies blockading PD-1/PD-Ls axis have achieved good effect and received Food and Drug Administration approval. The role of PD-1/PD-Ls in tumors has been well studied, but little is known on the mechanism by which PD-1 blocks T-cell activation. In this study, we provide a brief overview on the discovery and regulatory mechanism of PD-1 and PD-L1 dysregulation in tumors, as well as the function and signaling pathway of PD-1 and its ligands; their roles in tumor evasion and clinical treatment were also studied.

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The role of programmed cell death‐1 (PD‐1) and its ligands in pediatric cancer

Dam

Zwart

Meyer‐Wentrup

2014

Pediatric Blood & Cancer

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Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2 maintain self-tolerance and modulate physiological immune responses. Recently, targeting the PD-1/PD-L1 pathway with blocking antibodies has emerged as a potentially promising approach to treat advanced cancers in adult patients. Since tumor PD-L1 expression is currently considered the most important predictive biomarker for successful checkpoint blockade, we summarize expression data for the most common tumors of childhood. Additionally, we give an introduction into PD-1 function in the immune system to then focus on PD-1 mediated tumor immune escape. Pediatr Blood Cancer 2015;62:190-197. © 2014 Wiley Periodicals, Inc.

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Interferon‐induced programmed death‐ligand 1 (PD‐L1/B7‐H1) expression increases on human acute myeloid leukemia blast cells during treatment

Abstract: Our observations support the recently suggested PD-L1-mediated adaptive immune resistance and argue for a targeting of the PD-L1/PD-1 pathway during the consolidation phase of AML treatment.

Cited by 94 publications

References 46 publications

Programmed death-1 checkpoint blockade in acute myeloid leukemia

Programmed death-1 checkpoint blockade in acute myeloid leukemia

PD-1 and its ligands are important immune checkpoints in cancer

The role of programmed cell death‐1 (PD‐1) and its ligands in pediatric cancer

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