fig1

Figure 1. EMP affects various steps of the cancer-immunity cycle. The therapeutic rationale for targeting EMP in combination with ICB is based on the fact that EMP affects multiple steps of the cancer-immunity cycle described by Chen and Mellman^[117]. Briefly, targeting EMP can induce an increased release of DAMPs serving as an adjuvant during the release of cancer cell antigens (STEP 1). DAMPs are further recognized by pattern recognition receptors (PRRs) including TLRs. EMP targeting can induce an M1 to M2 polarization of macrophages and an activation of APCs, and thus aid in cancer antigen presentation (STEP 2). Targeting EMP and the EMP-associated immunosuppressive tumor immune microenvironment (TIME) can enable the infiltration of educated T cells into the cancer (STEP 5). EMP is associated with reduced recognition (STEP 6) and immune effector cell-mediated killing (STEP 7) of cancer cells, and targeting EMP can therefore induce increased effector cell-mediated lysis of cancer cells and propagation of the cycle. Adapted courtesy of Chen and Mellman^[117]. EMP: epithelial-mesenchymal plasticity; ICB: immune checkpoint blockade; DAMPs: damage-associated molecular patterns; APCs: antigen-presenting cells