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Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids

Tumor-associated macrophages (TAMs) and monocytes that accumulate in colorectal cancer (CRC) play a crucial role in shaping the tumor microenvironment (TME) and anti-tumor immune responses. Although TAMs have been linked to both pro- and anti-tumor functions, our understanding of the cues instructin...

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Main Authors: Balzasch, Bianca M. (Author) , Kries, Andreas von (Author) , Hüll, Saskia (Author) , Shaltiel, Indra A. (Author) , Boonekamp, Kim E. (Author) , Ast, Volker (Author) , Burgermeister, Elke (Author) , Betge, Johannes (Author) , Ebert, Matthias (Author) , Boutros, Michael (Author) , Helming, Laura (Author) , Umansky, Viktor (Author) , Cerwenka, Adelheid (Author)
Format: Article (Journal)
Language:English
Published: 22 Feb 2026
In: OncoImmunology
Year: 2026, Volume: 15, Issue: 1, Pages: 1-19
ISSN:2162-402X
DOI:10.1080/2162402X.2026.2633012
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1080/2162402X.2026.2633012
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Author Notes:Bianca M. Balzasch, Andreas von Kries, Saskia Hüll, Indra A. Shaltiel, Kim E. Boonekamp, Volker Ast, Elke Burgermeister, Johannes Betge, Matthias Ebert, Michael Boutros, Laura Helming, Viktor Umansky and Adelheid Cerwenka
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Summary:Tumor-associated macrophages (TAMs) and monocytes that accumulate in colorectal cancer (CRC) play a crucial role in shaping the tumor microenvironment (TME) and anti-tumor immune responses. Although TAMs have been linked to both pro- and anti-tumor functions, our understanding of the cues instructing their heterogeneous phenotypes and function in cancer patients remains limited. Here, we established co-cultures comprising primary human monocytes and patient-derived organoids (PDOs) from patients with microsatellite-stable CRC to emulate myeloid/tumor cell interactions in vitro. Upon encountering PDOs, monocytes acquire phenotypic changes that are distinct from those induced by typical polarization protocols. Single-cell RNA sequencing revealed that PDO-exposed monocytes transcriptionally resembled IL1B-programmed monocytes previously identified in the tumor tissues of CRC patients. This phenotype emerged independently of tumor mutational profiles or consensus molecular subtypes. Mechanistically, soluble PDO-derived mediators induced the production of CXCL2, CXCL5 and CXCL7 chemokines, whereas the phagocytic uptake of tumor debris impaired the MHC class II-mediated antigen presentation capabilities of monocytes in co-culture. In addition, our in vitro system allowed functional assessment of PDO-exposed monocytes demonstrating a compromised capacity to mount an inflammatory response upon TLR stimulation. Together, PDO-monocyte co-cultures offer a platform to dissect the interplay between cancer cells and monocytes, and advance our understanding of myeloid plasticity and function in cancer patients.
Item Description:Gesehen am 12.03.2026
Physical Description:Online Resource
ISSN:2162-402X
DOI:10.1080/2162402X.2026.2633012

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