In-vitro Modulation of mTOR-HIF-1α Axis by TLR7/8 Agonist (Resiquimod) in B-Chronic Lymphocytic Leukemia

Targeting toll-like receptors (TLRs), via TLR agonists, has been implicated in the regulation of immunometabolism. B-chronic lymphocytic leukemia (B-CLL) represents a suitable model for B-cell derived malignancies with shifted metabolic adaptations. Several signaling pathways have been found to be c...

Full description

Saved in:

Bibliographic Details
Published in:	Indian journal of hematology & blood transfusion Vol. 39; no. 4; pp. 537 - 545
Main Authors:	Hanafy, Rana M., Demian, Soheir R., Abou-Shamaa, Lobna A., Ghallab, O., Osman, Eman M.
Format:	Journal Article
Language:	English
Published:	New Delhi Springer India 01-10-2023 Springer Nature B.V
Subjects:	Blood Transfusion Medicine Gene expression Hematology Human Genetics Leukemia Medicine Medicine & Public Health Metabolism Oncology Original Original Article Targeted cancer therapy mTOR Immunometabolism HIF-1α B cells TLR7/8 agonist B-CLL
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Targeting toll-like receptors (TLRs), via TLR agonists, has been implicated in the regulation of immunometabolism. B-chronic lymphocytic leukemia (B-CLL) represents a suitable model for B-cell derived malignancies with shifted metabolic adaptations. Several signaling pathways have been found to be critical in metabolic reprogramming of CLL, including mechanistic target of rapamycin- hypoxia inducible factor-1α (mTOR- HIF-1α) pathway, the main metabolic regulator of glycolysis. Here, we investigated the effect of TLR7/8 agonist (Resiquimod) on the expression of mTOR and HIF-1α in patients with CLL. B cells were purified using Rosettesep Human B cell Enrichment Cocktail (Stem cell Technologies, Vancouver, BC, Canada#15,024) from peripheral venous blood of CLL patients (n = 20) and healthy individuals (n = 15). Isolated B cells were then cultured in both presence and absence of Resiquimod. Gene expression of mTOR and HIF-1α were assessed using qRT-PCR. Resiquimod significantly decreased mTOR and HIF-1α gene expression in both CLL ( p < 0.001and p < 0.001, respectively) and Normal B cells ( p = 0.004 and p = 0.001, respectively). Resiquimod may reprogram immunometabolism of malignant B-CLL cells via down-regulation of key glycolytic metabolic actors, mTOR and HIF-1α genes. Accordingly, Resiquimod may be an adjuvant as a therapeutic tool for CLL, which needs to be studied further.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0971-4502 0974-0449 0974-0449 0971-4502
DOI:	10.1007/s12288-023-01649-y