Interactions between MFAP5 + fibroblasts and tumor-infiltrating myeloid cells shape the malignant microenvironment of colorectal cancer

• Published in: Journal of translational medicine 2023-06, Vol.21 (1), p.405-405, Article 405
• Main Authors: Peng, Zhiwei, Ren, Zihao, Tong, Zhiwei, Zhu, Yinan, Zhu, Yansong, Hu, Kongwang
• Format: Article
• Language: English
• Subjects: Analysis; Care and treatment; Colorectal cancer; Colorectal Neoplasms - genetics; Development and progression; Fibroblasts; Fibroblasts - pathology; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Macrophages; Metastasis; MFAP5; Myeloid Cells - pathology; Prevention; Risk factors; RNA sequencing; Signal Transduction; Single cell RNA-sequencing; Spatial transcriptomics; Tumor Microenvironment - genetics
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04281-6

The therapeutic targeting of the tumor microenvironment (TME) in colorectal cancer (CRC) has not yet been fully developed and utilized because of the complexity of the cell-cell interactions within the TME. The further exploration of these interactions among tumor-specific clusters would provide more detailed information about these communication networks with potential curative value. Single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing datasets were integrated in this study to explore the biological properties of MFAP5 + fibroblasts and their interactions with tumor-infiltrating myeloid cells in colorectal cancer. Immunohistochemistry and multiplex immunohistochemistry were performed to confirm the results of these analyses. We profiled heterogeneous single-cell landscapes across 27,414 cells obtained from tumors and adjacent tissues. We mainly focused on the pro-tumorigenic functions of the identified MFAP5 + fibroblasts. We demonstrated that tumor-resident MFAP5 + fibroblasts and myeloid cells (particularly C1QC + macrophages) were positively correlated in both spatial transcriptomics and bulk RNA-seq public cohorts. These cells and their interactions might shape the malignant behavior of CRC. Intercellular interaction analysis suggested that MFAP5 + fibroblasts could reciprocally communicate with C1QC + macrophages and other myeloid cells to remodel unfavorable conditions via MIF/CD74, IL34/CSF1R, and other tumor-promoting signaling pathways. Our study has elucidated the underlying pro-tumor mechanisms of tumor-resident MFAP5 + fibroblasts and provided valuable targets for the disruption of their properties.