%0 Journal Article
%A Balzasch, Bianca M
%A von Kries, Andreas
%A Hüll, Saskia
%A Shaltiel, Indra A
%A Boonekamp, Kim Elisabeth
%A Ast, Volker
%A Burgermeister, Elke
%A Betge, Johannes
%A Ebert, Matthias
%A Boutros, Michael
%A Helming, Laura
%A Umansky, Viktor
%A Cerwenka, Adelheid
%T Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.
%J OncoImmunology
%V 15
%N 1
%@ 2162-4011
%C Abingdon
%I Taylor & Franics
%M DKFZ-2026-00411
%P 2633012
%D 2026
%X 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.
%K Humans
%K Organoids: pathology
%K Organoids: immunology
%K Organoids: metabolism
%K Monocytes: immunology
%K Monocytes: metabolism
%K Monocytes: pathology
%K Interleukin-1beta: metabolism
%K Colonic Neoplasms: pathology
%K Colonic Neoplasms: immunology
%K Colonic Neoplasms: metabolism
%K Colonic Neoplasms: genetics
%K Tumor Microenvironment: immunology
%K Coculture Techniques
%K Tumor-Associated Macrophages: immunology
%K Tumor-Associated Macrophages: metabolism
%K IL1B (Other)
%K Organoid (Other)
%K colon cancer (Other)
%K tumor-associated macrophages (Other)
%K Interleukin-1beta (NLM Chemicals)
%K IL1B protein, human (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41723598
%R 10.1080/2162402X.2026.2633012
%U https://inrepo02.dkfz.de/record/309998