Fig. 8. Schematic for the mechanisms by which BRCA1 deficiency in breast cancer formation and improves responses to anti–PD1 antibody.

In BRCA1 deficiency epithelial cells, S100A9 expression level constantly increases in early stages and secrets out to recruit and activate MDSCs, which creates an immunosuppression microenvironment by inhibit expansion and activation of T cells. This process can be further enhanced by CXCL12 that positively regulated by S100A9 and form a positive feedback loop. And this immunosuppression microenvironment is beneficial for tumor growth. The inhibitors of S100A9 and CXCL12, Tasquinimod and AMD3465, combine with anti-PD1 antibody can rescue the immunosuppression microenvironment and repress tumor growth. Green arrows indicate a decrease; red arrows indicate an increase.