Journal Article

DKFZ-2026-00411

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids.

Balzasch, B. M. ; von Kries, A. ; Hüll, S. ; Shaltiel, I. A. ; Boonekamp, K. E.DKFZ* ; Ast, V. ; Burgermeister, E. ; Betge, J.DKFZ* ; Ebert, M. ; Boutros, M.DKFZ* ; Helming, L. ; Umansky, V.DKFZ* ; Cerwenka, A.

2026
Taylor & Franics Abingdon

Abstract: 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.

Keyword(s): Humans (MeSH) ; Organoids: pathology (MeSH) ; Organoids: immunology (MeSH) ; Organoids: metabolism (MeSH) ; Monocytes: immunology (MeSH) ; Monocytes: metabolism (MeSH) ; Monocytes: pathology (MeSH) ; Interleukin-1beta: metabolism (MeSH) ; Colonic Neoplasms: pathology (MeSH) ; Colonic Neoplasms: immunology (MeSH) ; Colonic Neoplasms: metabolism (MeSH) ; Colonic Neoplasms: genetics (MeSH) ; Tumor Microenvironment: immunology (MeSH) ; Coculture Techniques (MeSH) ; Tumor-Associated Macrophages: immunology (MeSH) ; Tumor-Associated Macrophages: metabolism (MeSH) ; IL1B ; Organoid ; colon cancer ; tumor-associated macrophages ; Interleukin-1beta ; IL1B protein, human

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Contributing Institute(s):

1. B110 Signalwege funktionelle Genomik (B110)
2. NWG-KKE Translationale Gastrointestinale Onkologie und präklinische Modelle (B440)
3. KKE Dermatoonkologie (A370)

Research Program(s):

1. 319H - Addenda (POF4-319H) (POF4-319H)

Appears in the scientific report 2026

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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