Evaluation of triple negative breast cancer with heterogeneous immune infiltration
This research is the first one to measure differences in immune heterogeneity within the same patient, avoiding patients' inter-heterogeneity, for the study of potential casualties to the presence of infiltrating immune cells. This difference could be explained due to the tumor intrinsic characteristics (for example, their HLA -human leukocyte antigen- phenotype having different affinity for antigens). However, here we have shown that it may depend also on the tumor heterogeneity. Secretion of different proteins and enzymes, transcriptional alterations, and expression of different regulatory genes and oncogenes by the tumor cells can lead to immune recognition and infiltration in some areas but not in others. This observation is reflected in the differential expression analysis in each patient as well as in the gene set enrichment analysis, in which, on top of the upregulation of the immune pathways in the high TIL areas, there is an upregulation of other non-immune related pathways. We hypothesized that the differences in the gene expression between the two areas are due to intrinsic differences between the tumor cells of each area that evolve differently during tumor development. The team recommends future research with single cell sequencing in patients with the same characteristics.
Steps to reproduce
The steps and scripts to reproduce are described in: https://github.com/jfnavarro/RNASEQ_TNBC