In this regard, it is also of particular interest that the PTIS was found to be enriched in non-tumor populations such as macrophages and T cells of Merkel cell carcinoma patients treated with avelumab (Fig. 3E)—suggesting PD-L1 inhibition can likely induce ‘off-target’ host effects that can have negative effects on treatment efficacy (Mastri et al, 2018a). Here, CD274 is linked to Merkel cell skin cancer.