Extensive Phenotypic Characterization of T Cells Infiltrating Liver Metastasis from Colorectal Cancer: A Potential Role in Precision Medicine

SIMPLE SUMMARY: Cancer cell progression and establishment at the secondary site are influenced by the immune system, meaning that its characterization is crucial to target the metastatic process in oncological patients. As liver metastasis is the principal cause of death in colorectal cancer (CRC) patients, discovering which functional T-cell subsets are present will possibly unravel new targets in the tumor microenvironment. In this study, we characterized several T-cell populations by flow cytometry in non-tumor and tumor samples of CRC liver metastasis, both subdivided according to their growth pattern into desmoplastic and non-desmoplastic. A tendency toward an immunosuppressive microenvironment has been noted, but we also found a significant increase in follicular cytotoxic T cells. Further studies are crucial for fully characterizing the molecular mechanisms involved in CRC liver metastasis formation. Our findings, however, identify new prospective targets to treat these patients. ABSTRACT: Colorectal cancer (CRC) is one of the most common cancers worldwide, with liver metastasis being its main cause of death. This study harvested fresh biological material from non-tumor and tumor tissue from 47 patients with CRC liver metastasis after surgery, followed by mechanical cellular extraction and stain-lyse-wash direct immunofluorescence technique. Here, 60 different T-cell populations were characterized by flow cytometry. Tumor samples were also subdivided according to their growth pattern into desmoplastic and non-desmoplastic. When we compared tumor versus non-tumor samples, we observed a significantly lower percentage of T-lymphocyte infiltration in the tumor in which the CD4(+) T-cell density increased compared to the CD8(+) T cells. T regulatory cells also increased within the tumor, even with an activated phenotype (HLA-DR(+)). A higher percentage of IL-17-producing cells was present in tumor samples and correlated with the metastasis size. In contrast, we also observed a significant increase in CD8(+) follicular-like T cells (CD185(+)), suggesting a cytotoxic response to cancer cells. Additionally, most infiltrated T cells exhibit an intermediate activation phenotype (CD25(+)). In conclusion, our results revealed potential new targets and prognostic biomarkers that could take part in an algorithm for personalized medicine approaches improving CRC patients’ outcomes.