Dendritic cell profile in tumoral microenvironment of human breast carcinomas

Abstract

Argentina has the second-highest mortality rate for breast cancer (BC) in South America. The immune cells present in the tumor microenvironment (TME) perform dual functions, being able to eliminate or promote malignancy according to the signals present. We believe that the dendritic cells (DCs) found in the TME play a fundamental role in the development of the mammary tumor. Our hypothesis is that there are different subpopulations and maturation profiles of DCs in the TME, and these profiles are associated with tumor traits of mammary carcinomas. Initially, we propose as a general objective to study the different types of DCs present in the TME and to determine the profile of these different subtypes in human breast carcinomas. Methodology: Once the tumors were obtained by surgery, breast carcinoma-derived fractions were mechanically and enzymatically disaggregated. Tumoral (EpCAM+) and non-tumoral (EpCAM-) populations of each fraction were isolated using cell sorting flow cytometry. DC populations were characterized by flow cytometry using the HLA-DR, CD14, CD11c, CD1c cell surface markers to perform the gating strategy. Results: We obtained tumoral and non-tumoral populations derived from eight human breast carcinomas fractions. We defined four different DC subpopulations present in the TME: pDCs, inflammatory DCs, cCD1 and cCD2 DCs. Interestingly, we observed that each tumoral fraction has a unique DC profile, according to the high heterogeneity already described for this type of tumor. Based on the tumor cohort analysis, we evidenced a negative correlation between tumor cells and cDC2 DC populations (r= -0.76, p<0.027). Conclusion: Breast TME contains different DC profiles associated with tumoral cell proportions in human breast carcinoma fractions. Ongoing and future experiments will allow us to determine the maturation profiles of these DCs and analyze their relationship with genomic/epigenomic and clinicopathological tumor characteristics.