Innate Immune Cells in the Tumor Microenvironment of Liver Metastasis from Colorectal Cancer: Contribution to a Comprehensive Therapy

Author:

Sampaio-Ribeiro Gabriela123ORCID,Ruivo Ana45,Silva Ana1,Santos Ana Lúcia1,Oliveira Rui Caetano2678,Gama João9ORCID,Cipriano Maria Augusta9,Tralhão José Guilherme24578,Paiva Artur12310ORCID

Affiliation:

1. Flow Cytometry Unit, Clinical Pathology Department, Centro Hospitalar e Universitário de Coimbra EPE, 3000-075 Coimbra, Portugal

2. Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

3. Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal

4. Surgery Department, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal

5. Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

6. Germano de Sousa—Centro de Diagnóstico Histopatológico CEDAP, 3000-377 Coimbra, Portugal

7. Centre of Investigation on Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal

8. Clinical and Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal

9. Pathology Department, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, Portugal

10. Ciências Biomédicas Laboratoriais, ESTESC—Coimbra Health School, Instituto Politécnico de Coimbra, 3046-854 Coimbra, Portugal

Abstract

Colorectal 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.

Funder

FCT

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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