Spatial interactions between macrophages and T cells in breast cancer tumour microenvironment

Abstract

Tumour-associated macrophages (TAMs) are the most abundant and heterogeneous im- mune population in the breast cancer tumour microenvironment (TME). They mediate diverse pro-tumorigenic actions and their abundance is associated with poor prognosis in patients. Previous studies identified SIGLEC1 and CCL8 as two molecules upregulated in BC-associated macrophages and involved in mediating TAM recruitment and expansion in human breast cancer TME. The overexpression of both molecules is associated with worse prognosis.

However, the interactions of TAMs expressing SIGLEC1 and CCL8 (DPMF) with other TME components remained yet to be elucidated. Here, this project identified detailed molecular features to characterise DPMF via re-analyses of the human breast cancer single-cell atlas (Wu et al., 2021). The survival analyses performed in the bulk transcriptomics datasets of large breast cancer patient cohorts validated that DPMF abundances are associated with worse clinical prognosis (Curtis et al., 2012). Analyses in publicly available triple-negative breast cancer spatial transcriptomics datasets identi- fied a broad immunosuppressive TME associated with DPMF presence. Through further quantitative pathology analyses in whole-slide multiplex images of various spontaneous murine breast cancer models, it is identified that the depletion of SIGLEC1 and CCL8 re-potentiate the infiltration of cytotoxic T cells and T helper cells in relatively late stage of the cancer progression. In summary, this study highlights DPMFs as an immunosup- pressive macrophage subset in breast cancer tumour microenvironment. The depletion of their cellular activities can re-activate the T cells infiltration in the late cancer stages and may be associated with therapeutic implications.