Immune modulatory effects of Idelalisib in stromal cells of chronic lymphocytic leukemia

Handl SA, Von Heydebrand F, Völkl S, Oostendorp RAJ, Wilke J, Kremer A, Mackensen A, Lutzny-Geier G (2021)

Publication Type: Journal article

Publication year: 2021

Journal

DOI: 10.1080/10428194.2021.1927019

Abstract

Molecular targets of tyrosine kinase inhibitors are not restricted to the B-cell compartment but also regulate functions in the tumor microenvironment. Increasing evidence suggests that B-cell receptor-associated kinases like protein kinase C (PKC)-beta is essential for the formation of a microenvironment supporting leukemic growth. Here we describe the effect of Idelalisib on the PKC beta/NF-kappa B and Notch pathway in stromal cells upon contact to primary chronic lymphocytic leukemia cells (CLL). There is no Idelalisib-dependent regulation of the Notch expression in stromal cells, whereas Idelalisib induces PKC beta expression and activates the canonical NF-kappa B pathway. Idelalisib deregulates important immune-modulatory proteins in activated stromal cells, which might provoke the patient's side effects. Additionally, we established a 3D-stroma/leukemia model, that can give us a more defined look into the communication between tumor and stromal cells than standard cell cultures. This opens up the possibility to improve therapies, especially in the context of minimal-residual disease.

Authors with CRIS profile

Involved external institutions

Technische Universität München (TUM) Germany (DE)

How to cite

APA:

Handl, S.A., Von Heydebrand, F., Völkl, S., Oostendorp, R.A.J., Wilke, J., Kremer, A.,... Lutzny-Geier, G. (2021). Immune modulatory effects of Idelalisib in stromal cells of chronic lymphocytic leukemia. Leukemia & Lymphoma. https://doi.org/10.1080/10428194.2021.1927019

MLA:

Handl, Sarah Annika, et al. "Immune modulatory effects of Idelalisib in stromal cells of chronic lymphocytic leukemia." Leukemia & Lymphoma (2021).

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