The immunogram of inflammatory breast cancer.

Inflammatory breast cancer (IBC) is the most aggressive and fatal clinical presentation of breast cancer. Despite the term "inflammatory", based on the clinical presentation, IBC is biologically driven by an immunosuppressive tumor microenvironment (TME). Whether IBC can be switched into an immune-inflamed TME by immune-checkpoint inhibitors (ICIs) is a matter of debate. Presently, measurable biomarkers of IBC-TME have never been synthetized into a comprehensive portray of the immune-milieu (i.e., an immunogram), describing the immune-vulnerability of IBC and potentially predicting the response to ICIs. We propose an immunogram for IBC, based on preclinical and clinical studies, including six parameters: the presence of immune-effector cells, of immune-suppressive cells and of immune checkpoints, the general immune status, the activation of immune-suppressive pathways, the tumor foreignness. The IBC immunogram suggests the existence of a preexisting immune TME that is suppressed by mechanisms of immune-escape but might be restored by ICIs. The combination of chemotherapy and ICIs in patients with IBC is based on a strong biological rationale. However, the design and the development of clinical trials assessing the incorporation of ICIs raise many methodological and practical issues. In parallel with the further comprehension of IBC biology, the prospective validation and integration of biomarkers predictive of response to ICIs are warranted.