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000309998 1001_ $$aBalzasch, Bianca M$$b0
000309998 245__ $$aMonocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.
000309998 260__ $$aAbingdon$$bTaylor & Franics$$c2026
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000309998 520__ $$aTumor-associated macrophages (TAMs) and monocytes that accumulate in colorectal cancer (CRC) play a crucial role in shaping the tumor microenvironment (TME) and anti-tumor immune responses. Although TAMs have been linked to both pro- and anti-tumor functions, our understanding of the cues instructing their heterogeneous phenotypes and function in cancer patients remains limited. Here, we established co-cultures comprising primary human monocytes and patient-derived organoids (PDOs) from patients with microsatellite-stable CRC to emulate myeloid/tumor cell interactions in vitro. Upon encountering PDOs, monocytes acquire phenotypic changes that are distinct from those induced by typical polarization protocols. Single-cell RNA sequencing revealed that PDO-exposed monocytes transcriptionally resembled IL1B-programmed monocytes previously identified in the tumor tissues of CRC patients. This phenotype emerged independently of tumor mutational profiles or consensus molecular subtypes. Mechanistically, soluble PDO-derived mediators induced the production of CXCL2, CXCL5 and CXCL7 chemokines, whereas the phagocytic uptake of tumor debris impaired the MHC class II-mediated antigen presentation capabilities of monocytes in co-culture. In addition, our in vitro system allowed functional assessment of PDO-exposed monocytes demonstrating a compromised capacity to mount an inflammatory response upon TLR stimulation. Together, PDO-monocyte co-cultures offer a platform to dissect the interplay between cancer cells and monocytes, and advance our understanding of myeloid plasticity and function in cancer patients.
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000309998 650_7 $$2Other$$aIL1B
000309998 650_7 $$2Other$$aOrganoid
000309998 650_7 $$2Other$$acolon cancer
000309998 650_7 $$2Other$$atumor-associated macrophages
000309998 650_7 $$2NLM Chemicals$$aInterleukin-1beta
000309998 650_7 $$2NLM Chemicals$$aIL1B protein, human
000309998 650_2 $$2MeSH$$aHumans
000309998 650_2 $$2MeSH$$aOrganoids: pathology
000309998 650_2 $$2MeSH$$aOrganoids: immunology
000309998 650_2 $$2MeSH$$aOrganoids: metabolism
000309998 650_2 $$2MeSH$$aMonocytes: immunology
000309998 650_2 $$2MeSH$$aMonocytes: metabolism
000309998 650_2 $$2MeSH$$aMonocytes: pathology
000309998 650_2 $$2MeSH$$aInterleukin-1beta: metabolism
000309998 650_2 $$2MeSH$$aColonic Neoplasms: pathology
000309998 650_2 $$2MeSH$$aColonic Neoplasms: immunology
000309998 650_2 $$2MeSH$$aColonic Neoplasms: metabolism
000309998 650_2 $$2MeSH$$aColonic Neoplasms: genetics
000309998 650_2 $$2MeSH$$aTumor Microenvironment: immunology
000309998 650_2 $$2MeSH$$aCoculture Techniques
000309998 650_2 $$2MeSH$$aTumor-Associated Macrophages: immunology
000309998 650_2 $$2MeSH$$aTumor-Associated Macrophages: metabolism
000309998 7001_ $$00000-0002-7425-2329$$avon Kries, Andreas$$b1
000309998 7001_ $$aHüll, Saskia$$b2
000309998 7001_ $$00000-0002-5673-6741$$aShaltiel, Indra A$$b3
000309998 7001_ $$0P:(DE-He78)a1fe2ba34f6963f2462d1c670b4c206d$$aBoonekamp, Kim Elisabeth$$b4$$udkfz
000309998 7001_ $$aAst, Volker$$b5
000309998 7001_ $$00000-0002-4969-5697$$aBurgermeister, Elke$$b6
000309998 7001_ $$0P:(DE-He78)68cbca3e3973d332ccc4c6e31a76b10c$$aBetge, Johannes$$b7$$udkfz
000309998 7001_ $$aEbert, Matthias$$b8
000309998 7001_ $$0P:(DE-He78)3c0da8e3caa2aa50cad85152aa0465ad$$aBoutros, Michael$$b9$$udkfz
000309998 7001_ $$00009-0005-6268-2101$$aHelming, Laura$$b10
000309998 7001_ $$0P:(DE-He78)38be34240daf8b47325afc7910e77f7b$$aUmansky, Viktor$$b11$$udkfz
000309998 7001_ $$aCerwenka, Adelheid$$b12
000309998 773__ $$0PERI:(DE-600)2645309-5$$a10.1080/2162402X.2026.2633012$$gVol. 15, no. 1, p. 2633012$$n1$$p2633012$$tOncoImmunology$$v15$$x2162-4011$$y2026
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