Regional variation in the tumor microenvironment, immune escape and prognostic factors in breast cancer in sub-Saharan Africa.

The low overall survival rates of breast cancer (BC) patients in sub-Saharan Africa (SSA) are driven by regionally differing tumor biology, advanced tumor stages at diagnosis and limited access to therapy. However, it is not known whether regional differences in the composition of the tumor microenvironment (TME) exist and affect patients' prognosis. In this international, multicentre cohort study, 1,237 formalin-fixed, paraffin-embedded BC samples, including samples of the 'African Breast Cancer-Disparities in Outcomes (ABC-DO) Study', were analyzed. The immune cell phenotypes, their spatial distribution in the TME and immune escape mechanisms of BC samples from SSA and Germany (n=117) were investigated using histomorphology, conventional and multiplex immunohistochemistry (IHC), and RNA expression analysis. The data revealed no regional differences in the number of tumor-infiltrating lymphocytes (TILs) in the 1,237 SSA BC samples, while the distribution of TILs in different BC IHC subtypes showed regional diversity, particularly when compared to German samples. Higher TIL densities were associated with better survival in the SSA cohort (n=400), but regional differences concerning the predictive value of TILs existed. High numbers of CD163+ macrophages and CD3+CD8+ T cells accompanied by reduced cytotoxicity, altered IL10 and IFNγ levels and downregulation of MHC class I components were predominantly detected in BC samples from Western SSA. Features of non-immunogenic BC phenotypes were associated with reduced patient survival (n=131). We therefore conclude that regional diversity in the distribution of BC subtypes, TME composition and immune escape mechanisms should be considered for therapy decisions in SSA and the design of personalized therapies.