TY  - JOUR
AU  - Balzasch, Bianca M
AU  - von Kries, Andreas
AU  - Hüll, Saskia
AU  - Shaltiel, Indra A
AU  - Boonekamp, Kim Elisabeth
AU  - Ast, Volker
AU  - Burgermeister, Elke
AU  - Betge, Johannes
AU  - Ebert, Matthias
AU  - Boutros, Michael
AU  - Helming, Laura
AU  - Umansky, Viktor
AU  - Cerwenka, Adelheid
TI  - Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.
JO  - OncoImmunology
VL  - 15
IS  - 1
SN  - 2162-4011
CY  - Abingdon
PB  - Taylor & Franics
M1  - DKFZ-2026-00411
SP  - 2633012
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Organoids: pathology
KW  - Organoids: immunology
KW  - Organoids: metabolism
KW  - Monocytes: immunology
KW  - Monocytes: metabolism
KW  - Monocytes: pathology
KW  - Interleukin-1beta: metabolism
KW  - Colonic Neoplasms: pathology
KW  - Colonic Neoplasms: immunology
KW  - Colonic Neoplasms: metabolism
KW  - Colonic Neoplasms: genetics
KW  - Tumor Microenvironment: immunology
KW  - Coculture Techniques
KW  - Tumor-Associated Macrophages: immunology
KW  - Tumor-Associated Macrophages: metabolism
KW  - IL1B (Other)
KW  - Organoid (Other)
KW  - colon cancer (Other)
KW  - tumor-associated macrophages (Other)
KW  - Interleukin-1beta (NLM Chemicals)
KW  - IL1B protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41723598
DO  - DOI:10.1080/2162402X.2026.2633012
UR  - https://inrepo02.dkfz.de/record/309998
ER  -