Breast cancer develops in a complex microenvironment comprising several benign cell types and the extracellular matrix (which provides mechanical support for the tumour and enables cellular interaction in a paracrine fashion). The most abundant cell type is cancer-associated fibroblasts, but the breast cancer microenvironment also contains cells of leukocyte lineage (including lymphocytes, macrophages and myeloid-derived stromal cells), most of which are involved in the immune response.
Immunogenicity of breast cancer varies between the molecular subtypes, being highest in TNBC and HER2-positive tumours and lower in luminal A and luminal B subtypes. Moreover, the response to neoadjuvant treatment and the prognosis of breast cancer are positively influenced by the amount of tumour-infiltrating lymphocytes, which reflects the intensity of the immune response within the tumour bed.
The immune microenvironment influences the development and progression of breast cancer according to immune surveillance and immune editing principles. In the early phase of carcinogenesis, the immune microenvironment exerts mostly anti-tumour action, via the cytokine milieu derived from activated CD8+ and CD4+ T cells. By contrast, once a tumour becomes invasive, the microenvironment cell composition, including cancer-associated fibroblasts and cytokine content, are tumour-promoting, ‘hacked’ by breast cancer cells.