Characterisation of the immune contexture of breast cancer subtypes

Abstract

Purpose: The purpose and aim of this project was to investigate immune contexture according to tumour molecular subtype, and ER status. To find the interrelationship between serum cytokine levels and specific tumour cell infiltration levels. Material and methods: A newly released deconvolution tool called xCell, uses gene expression data to identify 64 different cell types present in the bulk tissue assessed for gene expression. We first validated the method by comparing xCell´s output with immune cell infiltration assessed by immunohistochemistry staining. The xCell profiles were then compared between the breast cancer molecular subtypes and ER status, to identify differences in the microenvironment. 26 immune cell profiles were compared to serum cytokine levels to find potential correlation between cell type levels and cytokine levels. Results: The findings suggest clear differences of levels of immune cells in the different subtypes and ER status. ER negative samples have higher immune infiltration compared to ER positive samples. Luminal A have higher level of epithelial cells and stroma cell when compared to the other subtypes. The Luminal B has higher immune infiltration of helper T cells and higher immune infiltration when compared to Luminal A and Normal-like. The Normal-like subtype has higher levels of stem cell like cells. Her2-enriched and the Basal-like subtype have the largest amount of immune infiltration compared to the other subtypes. When correlating immune cell levels to cytokine levels, we found that levels of PDGF-bb corelate to higher levels of B cells which may reflect lymphangiogenesis. Conclusion: These findings suggest that there are differences in the microenvironment of breast cancer subtypes. The method used to identify these findings should be better validated, as it only validates a small fraction of the cell types. In the future, a large validation using more markers, should be used. By further analysing the cell levels and infiltration profiles for individual subtypes, we could better understand the differences in the environment within a subtype. PDGF cytokine may be a good candidate for immunotherapy. These findings could potentially have prognostic and/or predictive value to deliver more targeted treatments.