Figure 2.

Multiplexed spatial protein profiling of adjuvanticity patterns in breast cancer. On the right side: The positive effects of regulated cell death and damage-associated molecular patterns (DAMPs) released in recruiting and activating dendritic cells (DCs), and tumor-associated macrophages (TAMs), in the tumor microenvironment (TME); further, phosphatidylserine (PS)-mediated activation of the complement system can stimulate B cells expression of ICOSL. On the left side: Some of the critical mechanisms of DAMP interference: (1) DAMPs’ downregulation: ATP concentrations can be limited by CD39/CD73 coordinated action, which can limit both ATP-induced adjuvanticity and favor adenosine-mediated immunosuppression; (2) indirect immune suppression: an indirect mechanism can interact with an effective priming, such as FOXP3+ regulatory T cell (Treg) differentiation, which can interfere with mature DC migration to tumor-draining lymph nodes (see DCs section); (3) alteration of DAMPs sensing machinery: STING downregulation can impair the sensing of free cytoplasmic DNA and thus STING-mediated IFN-γ signaling; (4) indirect interferences with DAMP signaling: CD47 expression can inhibit TAMs-mediated phagocytosis and therefore indirectly limit calreticulin and phosphatidylserine (PS) activity. CD55 can interfere with PS-induced complement-dependent cytotoxicity (CDC) and CDC-induced B cell differentiation into ICOSL+ B cells. Created with BioRender.com.