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Cross-disease integration of single-cell RNA sequencing data from lung myeloid cells reveals TAM signature in in vitro model

Title: Cross-disease integration of single-cell RNA sequencing data from lung myeloid cells reveals TAM signature in in vitro model
Authors: Catarina Pinto; Jakub Widawski; Sophie Zahalka; Barbara Thaler; Linda C. Schuster; Samuel W. Lukowski; Fidel Ramírez; Iñigo Tirapu
Source: OncoImmunology, Vol 14, Iss 1 (2025)
Publisher Information: Taylor & Francis Group
Publication Year: 2025
Collection: Directory of Open Access Journals: DOAJ Articles
Subject Terms: Single-cell RNA sequencing; tumor-associated macrophages; 3D human cell-based model; Immunologic diseases. Allergy; RC581-607; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; RC254-282
Description: Advancements in single-cell RNA sequencing (scRNA-seq) have revealed the phenotypic and functional diversity of tumor-associated macrophages (TAMs), identifying specific populations that directly impact the antitumor response. However, despite the recognition of TAMs as promising therapeutic targets for cancer treatment, research is hindered by the lack of validated human preclinical models. Here, we applied scRNA-seq to a 3D human cell-based model comprising tumor cell line-derived spheroids, cancer-associated fibroblasts and primary monocytes, a setup widely used in immuno-oncology research. Integration of our in vitro data with publicly available patient-derived datasets showed that the macrophages in this model share phenotypic characteristics with the pro-angiogenic and pro-fibrotic SPP1+ TAM population recently found across multiple cancer types and inflammatory lung diseases. This population was linked to aspects of disease progression and associated with poor prognosis in several tumor indications, highlighting the need for relevant models enabling its study as an immunotherapy target. Our research validates the use of a 3D human cell-based culture as a more in vivo-relevant model and enables the preclinical testing of novel macrophage-targeting drugs in a human disease-relevant setup.
Document Type: article in journal/newspaper
Language: English
Relation: https://doaj.org/toc/2162-402X; https://doaj.org/article/37960c1590924a3cadff7e0242a65005
DOI: 10.1080/2162402X.2025.2502278
Availability: https://doi.org/10.1080/2162402X.2025.2502278; https://doaj.org/article/37960c1590924a3cadff7e0242a65005
Accession Number: edsbas.D249B53F
Database: BASE