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024 7 _ |a 10.1080/2162402X.2026.2633012
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041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Balzasch, Bianca M
|b 0
245 _ _ |a Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.
260 _ _ |a Abingdon
|c 2026
|b Taylor & Franics
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520 _ _ |a 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.
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650 _ 7 |a IL1B
|2 Other
650 _ 7 |a Organoid
|2 Other
650 _ 7 |a colon cancer
|2 Other
650 _ 7 |a tumor-associated macrophages
|2 Other
650 _ 7 |a Interleukin-1beta
|2 NLM Chemicals
650 _ 7 |a IL1B protein, human
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Organoids: pathology
|2 MeSH
650 _ 2 |a Organoids: immunology
|2 MeSH
650 _ 2 |a Organoids: metabolism
|2 MeSH
650 _ 2 |a Monocytes: immunology
|2 MeSH
650 _ 2 |a Monocytes: metabolism
|2 MeSH
650 _ 2 |a Monocytes: pathology
|2 MeSH
650 _ 2 |a Interleukin-1beta: metabolism
|2 MeSH
650 _ 2 |a Colonic Neoplasms: pathology
|2 MeSH
650 _ 2 |a Colonic Neoplasms: immunology
|2 MeSH
650 _ 2 |a Colonic Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Colonic Neoplasms: genetics
|2 MeSH
650 _ 2 |a Tumor Microenvironment: immunology
|2 MeSH
650 _ 2 |a Coculture Techniques
|2 MeSH
650 _ 2 |a Tumor-Associated Macrophages: immunology
|2 MeSH
650 _ 2 |a Tumor-Associated Macrophages: metabolism
|2 MeSH
700 1 _ |a von Kries, Andreas
|0 0000-0002-7425-2329
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700 1 _ |a Hüll, Saskia
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700 1 _ |a Shaltiel, Indra A
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700 1 _ |a Boonekamp, Kim Elisabeth
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700 1 _ |a Ast, Volker
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700 1 _ |a Burgermeister, Elke
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700 1 _ |a Betge, Johannes
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700 1 _ |a Ebert, Matthias
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700 1 _ |a Boutros, Michael
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700 1 _ |a Umansky, Viktor
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700 1 _ |a Cerwenka, Adelheid
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773 _ _ |a 10.1080/2162402X.2026.2633012
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