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A co-stimulatory trap set by myeloid leukemia cells.

Esendagli G - Oncoimmunology (2013)

Bottom Line: The straightforward notion that tumor cells always exert immunosuppressive functions has been contradicted by the finding that myeloid leukemia cells can express potent co-stimulatory molecules.Indeed, the co-stimulatory support offered by leukemia cells can provoke helper T-cell responses.Unfavorably, this interaction allows leukemia cells to acquire immunosuppressive capacities.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Oncology; Hacettepe University Cancer Institute; Ankara, Turkey.

ABSTRACT
The straightforward notion that tumor cells always exert immunosuppressive functions has been contradicted by the finding that myeloid leukemia cells can express potent co-stimulatory molecules. Indeed, the co-stimulatory support offered by leukemia cells can provoke helper T-cell responses. Unfavorably, this interaction allows leukemia cells to acquire immunosuppressive capacities.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Co-stimulatory interactions between helper T cells and acute myeloid leukemia cells. (A) The initial engagement between acute myeloid leukemia (AML) cells that harbor B7-2 (CD86) and/or B7-H2 (ICOSL) provokes T-cell responses and TH1/TH17 differentiation. (B) In turn, helper T-cell responses modulate the expression of B7 family molecules on AML cells. In particular, B7-H2 levels are decreased while B7-H1 (PD-L1) and B7-DC (PD-L2) are upregulated. The AML cells gain immunosuppressive functions, hampering helper T-cell responses and favoring the differentiation of regulatory T cells, especially through the PD1 pathway.
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Figure 1: Figure 1. Co-stimulatory interactions between helper T cells and acute myeloid leukemia cells. (A) The initial engagement between acute myeloid leukemia (AML) cells that harbor B7-2 (CD86) and/or B7-H2 (ICOSL) provokes T-cell responses and TH1/TH17 differentiation. (B) In turn, helper T-cell responses modulate the expression of B7 family molecules on AML cells. In particular, B7-H2 levels are decreased while B7-H1 (PD-L1) and B7-DC (PD-L2) are upregulated. The AML cells gain immunosuppressive functions, hampering helper T-cell responses and favoring the differentiation of regulatory T cells, especially through the PD1 pathway.

Mentions: In our study, we conditioned a well-characterized AML cell line, namely, HL-60 cells, and were able to model the interaction between B7-2- and/or B7-H2-expressing leukemia cells and helper T cells.7 We obtained similar results with other myeloid leukemia cell lines. Under conditions of suboptimal stimulation of the T-cell receptor (TCR) complex, AML cells generated potent co-stimulatory signals that were required for helper T-cell responses.7 The upregulation of T-cell activation markers (e.g., CD154, CD25 and CD69), T-cell expansion, as well as the secretion of TH1 and TH17 cytokines including interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin (IL)-17A were the result of the interaction between helper T and AML cells, and co-stimulation was largely mediated by the B7-2+ AML cell subpopulation (Fig. 1).7


A co-stimulatory trap set by myeloid leukemia cells.

Esendagli G - Oncoimmunology (2013)

Figure 1. Co-stimulatory interactions between helper T cells and acute myeloid leukemia cells. (A) The initial engagement between acute myeloid leukemia (AML) cells that harbor B7-2 (CD86) and/or B7-H2 (ICOSL) provokes T-cell responses and TH1/TH17 differentiation. (B) In turn, helper T-cell responses modulate the expression of B7 family molecules on AML cells. In particular, B7-H2 levels are decreased while B7-H1 (PD-L1) and B7-DC (PD-L2) are upregulated. The AML cells gain immunosuppressive functions, hampering helper T-cell responses and favoring the differentiation of regulatory T cells, especially through the PD1 pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716749&req=5

Figure 1: Figure 1. Co-stimulatory interactions between helper T cells and acute myeloid leukemia cells. (A) The initial engagement between acute myeloid leukemia (AML) cells that harbor B7-2 (CD86) and/or B7-H2 (ICOSL) provokes T-cell responses and TH1/TH17 differentiation. (B) In turn, helper T-cell responses modulate the expression of B7 family molecules on AML cells. In particular, B7-H2 levels are decreased while B7-H1 (PD-L1) and B7-DC (PD-L2) are upregulated. The AML cells gain immunosuppressive functions, hampering helper T-cell responses and favoring the differentiation of regulatory T cells, especially through the PD1 pathway.
Mentions: In our study, we conditioned a well-characterized AML cell line, namely, HL-60 cells, and were able to model the interaction between B7-2- and/or B7-H2-expressing leukemia cells and helper T cells.7 We obtained similar results with other myeloid leukemia cell lines. Under conditions of suboptimal stimulation of the T-cell receptor (TCR) complex, AML cells generated potent co-stimulatory signals that were required for helper T-cell responses.7 The upregulation of T-cell activation markers (e.g., CD154, CD25 and CD69), T-cell expansion, as well as the secretion of TH1 and TH17 cytokines including interferon γ (IFNγ), tumor necrosis factor α (TNFα) and interleukin (IL)-17A were the result of the interaction between helper T and AML cells, and co-stimulation was largely mediated by the B7-2+ AML cell subpopulation (Fig. 1).7

Bottom Line: The straightforward notion that tumor cells always exert immunosuppressive functions has been contradicted by the finding that myeloid leukemia cells can express potent co-stimulatory molecules.Indeed, the co-stimulatory support offered by leukemia cells can provoke helper T-cell responses.Unfavorably, this interaction allows leukemia cells to acquire immunosuppressive capacities.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Oncology; Hacettepe University Cancer Institute; Ankara, Turkey.

ABSTRACT
The straightforward notion that tumor cells always exert immunosuppressive functions has been contradicted by the finding that myeloid leukemia cells can express potent co-stimulatory molecules. Indeed, the co-stimulatory support offered by leukemia cells can provoke helper T-cell responses. Unfavorably, this interaction allows leukemia cells to acquire immunosuppressive capacities.

No MeSH data available.


Related in: MedlinePlus