Featured Publication in Focus: Dual targeting of tumoral cells and immune microenvironment by blocking the IL-33/ IL1RL1 pathway

Authors:

Denggang Fu, Hua Jiang, Alan Long, Ella Harris, Hongfen Guo, Maegan L. Capitano, John Wrangle, Joshua R. Faust, Anilkumar Gopalakrishnapillai, Santhosh Kumar Pasupuleti, Baskar Ramdas, Reuben Kapur, Sonali P. Barwe,Nai-Kong V. Cheung  & Sophie Paczesny

 

Department of Microbiology and Immunology and Pediatrics, Medical University of South Carolina, Charleston, SC, USA.

 

nature communications.  nature

 

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Products referenced:

Catalogue # 101001PE

T1/ST2 (IL-33 R) Mouse, Monoclonal Antibody, PE Conjugated, 0.1 mL

 

ABSTRACT

Leukemia stem cells (LSCs) are a small yet powerful subset of leukemic cells that possess the ability to self-renew and have a long-term tumorigenic capa- city, playing a crucial role in both leukemia development and therapy resis- tance. These LSCs are influenced by external and internal factors within the bone marrow niche. By delving into the intricate interplay between LSCs and their immune environment, we can pave the way for innovative immu- notherapies that target both the malignant stem cells and the suppressive immune microenvironment, addressing both the “seed” and the “soil” simul- taneously. Through the analysis of public datasets and patient samples, we show that elevated IL1RL1 expression correlates with poor prognosis and therapy resistance in acute myeloid leukemia (AML). At the core of this pro- cess, stem cell leukemogenesis initiation and maintenance signals are driven by a stress-induced IL-33/IL1RL1 autocrine loop. This LSC-induced IL-33/IL1RL1 signaling fosters an immune regulatory microenvironment. Therefore, IL1RL1 emerges as a promising therapeutic target, with IL1RL1-specific T cell-engaging bispecific antibodies holding great potential as cutting-edge immunother- apeutics for AML.

 

 

 

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