Studies in animal models and in patients with colorectal cancer (CRC) recently demonstrated that tumor-associated macrophages (TAM) suppress growth of primary tumor and metastasis. Circulating monocytes are recruited to the growing tumor and constitute the main plastic resource of TAM. However, the role of programming of circulating monocytes in the functional polarization and activation of pro- and anti-tumor functions of TAM is poorly understood.
Peripheral blood monocytes of 22 CRC patients and 13 healthy donors were isolated by FACS. RNA was isolated and cDNA libraries were prepared. The whole-transcriptome profile of monocytes was determined by NGS. Bioinformatics analysis included standard technics, we used the Hallmark gene sets, Reactome, KEGG and GO databases for the presentation of NGS results. The study was carried out according to Declaration of Helsinki and was approved by the local committee of Medical Ethics.
We compared the transcriptome of monocytes from healthy donors and CRC patients. Using NES parameter> 1.5, we found the following transcriptional programs are activated in the monocytes of patients: LPS-mediated response, cell differentiation, regulation of cyclin-dependent kinases, iron transport, IL-4-dependent response, INFgamma-dependent response, angiogenesis, cell adhesion, leukocyte migration, chemotaxis, collagen formation. Transcriptional programs that are responsible for the histone acetylation, chromatin rearrangement and protein modification were suppressed in monocytes of CRC patients. The transcriptional profile of monocytes of patients with rectal cancer and colon cancer, when independently compared with monocytes of healthy donors, revealed similar groups of differentially expressed genes.
We identified new differential patterns of monocyte programming in CRC patients in comparison with healthy donors. Our data will allow us to clarify transcriptional and epigenetic mechanisms of anti-tumor TAM programming in CRC. The work was supported by the grant RSF 19-15-00151.
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National Research Tomsk State University.
Russian Science Foundation.
All authors have declared no conflicts of interest.