Simple SummaryIn this study, the role of cells of the innate immune system in the development and progression of colorectal cancer liver metastasis was investigated. Two proteins, CD274 (PD-L1) and CD206 (MRC1), have been associated with poor prognosis and disease progression. Our study analyzed tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis using flow cytometry to phenotypically characterize innate immune cells. Comparing tumor with non-tumor samples, we found an increase in CD274 expression on classical, intermediate, and, in a lower extension, non-classical monocytes. Interestingly, we observed a decrease in the percentage of all monocyte subpopulations expressing CD274 and CD206 in tumor samples with a desmoplastic growth pattern compared to non-desmoplastic. Moreover, a lower percentage of monocyte subpopulations expressing CD206 or CD274 was associated with increased disease-free survival. Our study suggests potential new targets and biomarkers for precision medicine to improve CRC patients’ outcomes.AbstractColorectal cancer (CRC) is the third most prevalent type of cancer, and liver metastasis is the most common site of metastatic development. In the tumor microenvironment (TME), various innate immune cells are known to influence cancer progression and metastasis occurrence. CD274 (PD-L1) and CD206 (MRC1) are proteins that have been associated with poor prognosis and disease progression. We conducted a study on tumoral and non-tumoral biopsies from 47 patients with CRC liver metastasis, using flow cytometry to phenotypically characterize innate immune cells. Our findings showed an increase in the expression of CD274 on classical, intermediate, and non-classical monocytes when comparing tumor with non-tumor samples. Furthermore, tumor samples with a desmoplastic growth pattern exhibited a significantly decreased percentage of CD274- and CD206-positive cells in all monocyte populations compared to non-desmoplastic samples. We found a correlation between a lower expression of CD206 or CD274 on classical, intermediate, and non-classical monocytes and increased disease-free survival, which points to a better prognosis for these patients. In conclusion, our study has identified potential new targets and biomarkers that could be incorporated into a personalized medicine approach to enhance the outcome for colorectal cancer patients.