Oncotarget: Activation of plasmacytoid dendritic cells promotes AML-cell fratricide

Oncotarget

published ”

Activation of plasmacytoid dendritic cells promotes AML-cell fratricide

” which reported that Interferons have been previously shown to aid in the clearance of AML cells. Type I interferons are produced primarily by plasmacytoid dendritic cells. However, these cells exist in a quiescent state in AML.

In addition, the authors showed increased expression of the immune-stimulatory receptor CD40. Then they next tested whether IFNβ would influence antibody-mediated fratricide among AML cells, as our recent work showed that AML cells could undergo cell-to cell killing in the presence of the CD38 antibody daratumumab.

These

Oncotarget

findings suggest that the tolerogenic phenotype of pDCs in AML can be reversed, and also demonstrate a possible means of enhancing endogenous Type I IFN production that would promote daratumumab-mediated clearance of AML cells.

These

Oncotarget

findings suggest that the tolerogenic phenotype of pDCs in AML can be reversed

Dr. Jonathan P. Butchar and Dr. Susheela Tridandapani both from

The Ohio State University

said, ”


Acute Myeloid Leukemia

(AML) is associated with defective innate and adaptive immune responses, as is seen with other malignancies.

”

Type I and Type II interferons have previously been tested in clinical trials for AML.

However, Type I interferons have not been examined as a dual-treatment with anti-CD38 within the context of AML.

Type I and Type II interferons signal through distinct pathways but there is also sufficient overlap to suggest that they may be of benefit when combined with daratumumab, and with fewer potential toxicities.

pDCs express TLR 7-9 and are able to produce many cytokines including TNF-α, CXCL8, and IL-6, but most importantly Type I Interferons after TLR stimulation.

In agreement with previous studies we found that R848 led to higher expression of CD40.

Notably, it also increased IFNβ production by AML-patient pDCs, and this induced an upregulation of CD38 in AML cells.

The Butchar/Tridandapani Research Team concluded in their


Oncotarget



Research Output

, ”

we report a novel mechanism of inducing the effector-like AML cell phenotype by reprogramming AML-patient pDCs to produce IFNβ through TLR stimulation. This can lead to upregulation of CD38 on AML cells and can enhance antibody-mediated fratricide of AML cells. These findings suggest that the use of either IFNβ or IFNβ-inducing agents in combination with an anti-CD38 therapeutic antibody could likely offer a new therapeutic option for AML.

”

###

DOI

–

https:/

/

doi.

org/

10.

18632/

oncotarget.

27949

Full text

–

https:/

/

www.

oncotarget.

com/

article/

27949/

text/

Correspondence to

– Jonathan P. Butchar –

[email protected]

and Susheela Tridandapani –

[email protected]

Keywords

–


plasmacytoid dendritic cells

,

interferon-beta

,

acute myeloid leukemia

,

fratricide

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Oncotarget

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