PD-L1 Is Expressed and Promotes the Expansion of Regulatory T Cells in Acute Myeloid Leukemia
| Autor: | Yuqing Dong, Yixiang Han, Yisha Huang, Songfu Jiang, Ziyang Huang, Rongrong Chen, Zhijie Yu, Kang Yu, Shenghui Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
PD-L1 lcsh:Immunologic diseases. Allergy Adult Male Adolescent medicine.medical_treatment Immunology chemical and pharmacologic phenomena acute myeloid leukemia interleukin-35 Lymphocyte Activation T-Lymphocytes Regulatory regulatory T cells B7-H1 Antigen 03 medical and health sciences Mice Young Adult 0302 clinical medicine Immune system PD-1 medicine Immunology and Allergy Animals Humans IL-2 receptor Original Research Aged biology Chemistry Myeloid leukemia FOXP3 hemic and immune systems Middle Aged Immune checkpoint Leukemia Myeloid Acute 030104 developmental biology Cytokine Interleukin 35 biology.protein Cancer research Female lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 11 (2020) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | Intratumoral accumulation of CD4+CD25+Foxp3+ regulatory T (Treg) cells occurs in acute myeloid leukemia (AML), but little is known about the role of tumor cells themselves in this process. Here, we showed that an immune checkpoint PD-L1 expressed by AML cells promoted the conversion and expansion of Treg cells sustaining high expression of Foxp3 and PD-1 as well as a suppressive function. Furthermore, an AML cell line HEL overexpressed PD-L1 promoted the conversion and expansion of Treg cells and CD4+PD-1+Foxp3+ T (PD-1+Treg) cells from the conventional CD4+ T cells. CD4+CD25highPD-1+ T cells secreted more IL-10 production than CD4+CD25highPD-1- T cells. IL-35, another cytokine secreted by Treg cells, promoted the proliferation of HL-60 cells and enhanced chemoresistance to cytarabine. Blockade of PD-1 signaling using anti-PD-L1 antibody dramatically impaired the generation of Treg cells and sharply retarded the progression of a murine AML model injected with C1498 cells. The frequency of intratumoral PD-1+ Treg cells was capable of predicting patient survival in patients with AML. In conclusion, our data suggest that PD-L1 expression by AML cells may directly drive Treg cell expansion as a mechanism of immune evasion and the frequency of PD-1+ Treg cells is a potential prognostic predictor in patients with AML. |
| Databáze: | OpenAIRE |
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