Figure 1. Impact of anatomical site on immunotherapy resistance.

Primary and metastatic breast tumors establish a number of immunosuppressive circuitries in support of disease progression and resistance to immunotherapy. Such immunosuppressive pathways (IP1, IP2, etc.) are generally multilayered in nature and differ between primary and metastatic disease sites, which considerably complicates the development of combinatorial therapeutic regimens that unlock the efficacy of immunotherapy. Interestingly, it seems that tumors of different histology developing at the same site rely on relatively similar immunosuppressive mechanisms for progressing and resisting treatment, pointing to a major role for anatomical location in the establishment of local immunosuppression. Please note that the relative contribution of IPs and site‐specific IPs (SSIPs) depicted here is for exemplifying purposes and does not reflect existing preclinical or clinical data.