CD8 + T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients

Wang, Meng-Jie; Bu, Jin; Zhou, Mi; Sido, Jessica M.; Lin, Yan‐Hui; Liu, Guanfang; Lin, Qiwen; Xu, Xiuzhang; Leavenworth, Jianmei W.; Shen, Erxia

doi:10.1016/j.clim.2017.08.021

Cited by 57 publications

(49 citation statements)

References 50 publications

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“…In acute myeloid leukemia, T cell exhaustion of bystander CD8þ lymphocytes has been discussed [52]. In SS patients, CD8þ cells down-regulate activation markers CD127/IL-7R and CD26 and remained unresponsive to IL-7 stimulation.…”

Section: Discussionmentioning

confidence: 99%

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Anzengruber

Ignatova

Schlaepfer

et al. 2019

Leukemia & Lymphoma

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In S ezary syndrome (SS) impaired T-cell function and cytokine profile lead to immune evasion. Immune checkpoints non-redundantly regulate immune responses and targeting them is promising. We evaluated the expression of BTLA, CTLA-4, FCRL3, LAG-3, and TIGIT in tumor and nontumor SS T-cells.Compared to CD4þ T helper cells from ten healthy individuals, tumor cells of eight SS patients had a significant upregulation of BTLA (1.5-fold; p < .0001), FRCL3 (2.2-fold; p < .0028) and TIGIT (2.2-fold; p < .0003) expression. In contrast, we found a reduced expression of LAG-3þ cells in the blood of tumor patients (0.5-fold; p < .0014). Only weak alternations between tumor, non-tumor cells, and healthy controls were observed regarding CTLA-4 (0.5-fold; p < .2022). Our results show a diverse expression pattern of immune-regulatory molecules in SS patients. As these molecules are essential in the regulation of T-cell mediated tumor surveillance and defense, their specific targeting might be of clinical relevance.

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Section: Discussionmentioning

confidence: 99%

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Anzengruber

Ignatova

Schlaepfer

et al. 2019

Leukemia & Lymphoma

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“…In AML patients, a large number of dysfunctional CD8 + T cells with increased expression of TIGIT and PD-1 but low levels of DNAM-1 was reported, but TIGIT expression in the NK cells of these patients has not been characterized. 38 As previously described, AML patients show low levels of DNAM-1 expression, while its ligands are highly expressed. 14 This could favor the binding of TIGIT with CD112 and CD155 ligands, promoting inhibitory signaling and, thereby, tumor immune escape.…”

Section: Expression Of Molecular Immune Checkpoint Inhibitorsmentioning

confidence: 81%

Acute myeloid leukemia and NK cells: two warriors confront each other

2018

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Acute myeloid leukemia (AML) is a heterogeneous disease whose therapies currently show elevated toxicity and a high rate of relapse. Recently, the burgeoning of new anti-tumor therapeutic strategies aimed at enhancing the immune response has pushed natural killer cells (NKs) into the spotlight. These cells are powerful warriors that can bring about the lysis of tumor cells through their cytotoxic ability. However, tumor cells have developed strategies to evade recognition mediated by NKs. Here, we review the mechanisms triggered by AML cells and discuss the emerging immunotherapeutic strategies that potentiate the anti-tumor functions of NKs. ARTICLE HISTORY

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“…Recent data have indicated that immune checkpoint blockade can improve T cell antileukemia effects in murine AML, providing the possibility of AML immunotherapy using immune checkpoint inhibitors. More recent studies have revealed that increased PD‐1+CD57+CD8+ T cells in AML patients, and increased PD‐1 + TIGIT + CD226 − CD8 + T cells result in CD8 + T cell dysfunction and are associated with poor clinical prognosis for patients with AML . However, the expression profiles of immune checkpoint receptors in different T cell subsets and T cell subfamilies from AML patients have not been clearly defined.…”

Section: Discussionmentioning

confidence: 99%

“…However, unlike B‐cell leukemia and lymphoma, the application of immunotherapy for acute myeloid leukemia (AML) has been limited due to limited understanding of global T cell immune dysfunction in AML . Multiple aspects of T cell dysfunction including lower activation, terminal proliferation, exhaustion, and senescence are functioning in AML at diagnosis, and impairment of T cell function might be mediated by up‐regulating immune checkpoint receptors, such as programmed death‐1 (PD‐1), lymphocyte‐activation gene 3, T‐cell immunoglobulin and mucin‐domain containing‐3 (Tim‐3) . For example, CD8+ T cell dysfunction in AML was in part reversible upon PD‐1 blockade in vitro, and PD‐1 blockade could enhance CD33‐CD3 BiTE antibody construct‐mediated cytotoxicity in AML .…”

Section: Introductionmentioning

confidence: 99%

“…at diagnosis, 8,9 and impairment of T cell function might be mediated by up-regulating immune checkpoint receptors, such as programmed death-1 (PD-1), lymphocyte-activation gene 3, T-cell immunoglobulin and mucin-domain containing-3 (Tim-3). [10][11][12][13] For example, CD8+ T cell dysfunction in AML was in part reversible upon PD-1 blockade in vitro, 7 and PD-1 blockade could enhance CD33-CD3 BiTE antibody construct-mediated cytotoxicity in AML. 14,15 Thus, it would be interesting to further characterize the complexity of AML-related T cell immunity, which might support the design of immunotherapies for AML.…”

Section: Introductionmentioning

confidence: 99%

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A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia

Huang

Tan

Chen

et al. 2019

Journal of Leukocyte Biology

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The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global T cell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR Vβ subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+T cells were increased in AML, particularly TCR Vβ2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death‐1 (PD‐1)+T cells in TCR Vβ subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD‐1+Vβ+T cells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD‐1+Vβ2+T cells with a high number of Vβ2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD‐1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+T cells were distributed in the AML‐M5 subtype group compared with the AML‐M3 group. In addition, higher PD‐1+ Vβ5.2+ and PD‐1+ Vβ12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD‐1+Vβ+T cells is a common characteristic of AML, higher PD‐1+Vβ2+T cells may be associated with a low antileukemia effect, and higher PD‐1+Vβ5.2+ and PD‐1+Vβ12+CD8+T cells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.

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CD8 + T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients

Cited by 57 publications

References 50 publications

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Divergent LAG-3 versus BTLA, TIGIT, and FCRL3 expression in Sézary syndrome

Acute myeloid leukemia and NK cells: two warriors confront each other

A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia

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