Dataset Information

Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids

ABSTRACT: Tumor-associated monocytes and macrophages (TAM) accumulate in colorectal cancer (CRC) and play an active role in shaping the tumor microenvironment (TME). While they have been linked to both pro- and anti-tumor functions, understanding the cues that instruct the phenotype of individual subsets as well as their functional impact on the TME remains challenging. In this study, we established co-cultures comprising primary human monocytes and patient-derived organoids (PDOs) from CRC tumors to emulate myeloid cell/carcinoma interactions in vitro that drive tumor-associated monocyte programming. Upon encountering PDOs, monocytes acquired a complex phenotype not reflected by classical TAM markers or polarization protocols. Single-cell RNA sequencing revealed that PDO-exposed monocyte transcriptionally resembled IL1B-programmed monocytes previously identified in CRC patients. This phenotype emerged independently of the tumors’ mutational profiles or CMS type. Mechanistically, soluble PDO-derived mediators induced the production of chemotactic CXCL2, CXCL5 and CXCL7, while phagocytic uptake of tumor debry limited the MHC class II-mediated antigen presentation capabilities of monocytes in co-culture. Additionally, our in vitro system allowed the functional assessment of PDO-exposed monocytes demonstrating a compromised capacity to mount an inflammatory response upon TLR stimulation. Together, our PDO–monocyte co-cultures offer a tractable, human-specific model system to study the interplay between epithelial cancer cells and monocytes, and advance our understanding of myeloid plasticity and function in cancer patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308548 | GEO | 2026/02/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:The interaction of neoplastic cells with their tumor microenvironment (TME) is required for cancer progression. However, in vitro cancer models, including recent in vitro 3-dimensional (3D) organoid cultures of primary human tumors, are typically comprised exclusively of neoplastic epithelium, with stromal and/or immune interactions requiring artificial reconstitution. As relevant to cancer immunotherapy, the unified co-culture of primary tumor epithelia with their endogenous, syngeneic tumor-infiltrating lymphocytes (TILs) as a cohesive unit has remained particularly elusive. Here, we used a single 3D air-liquid interface (ALI) methodology to successfully propagate 3D Patient-Derived Tumor Organoids (PDOs) as primary tumor epithelia together with native immune and myofibroblast stromal compartments without reconstitution. Derived from >100 diverse human surgically resected tumor samples or from murine tumors in syngeneic immunocompetent mice, PDOs preserved cancer histologic subtypes and mutational spectrum with endogenous T, B, NK cells and macrophages integrally embedded amidst the tumor epithelium. PDO-based TILs accurately recapitulated the T cell receptor (TCR) spectrum of the original tumors, as determined by a robust droplet-based immune profiling solution that links gene expression and immune repertoire in single cells. Anti-PD-1 or anti-PD-L1 treatment of organoids from murine tumors from syngeneic immunocompetent hosts induced activation and cytolytic activity of tumor antigen-specific TILs, indicating successful PDO modeling of immune checkpoint blockade (ICB) and anti-tumor immunity. Crucially, the anti-PD-1 antibody nivolumab activated TILs in PDOs from human lung, renal and melanoma clinical tumor resections. The organoid-based propagation of primary tumor epithelium en bloc with its endogenous immune stroma should facilitate mechanistic investigation of TME-specific local tumor immunity, with applications for functional testing of individualized patient immunotherapy responses.

Dataset Information

Monocytes acquire a tumor-associated IL1B program upon encountering patient-derived colon cancer organoids

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets