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Although T cells infiltrate melanomas, they usually fail to clear the tumor. Plasmacytoid DCs (PDCs) can regulate T-cell function and, in addition, can eliminate melanomas by TLR-mediated mechanisms. Vescovi et al. show that infiltration by PDCs occurs early in primary cutaneous melanoma and their localization is at the invasive margin, where the PDCs can interact with CD8⁺ T cells. However, in advanced and metastatic disease, PDCs do not infiltrate into tumor tissues and PDCs in circulation are reduced. This is due to a collapse of the PDC compartment during cancer progression, caused by soluble factors in the melanoma secretome that lead to PDC death and impaired differentiation from progenitor cells. These data highlight that rescuing PDCs could help in inducing antitumor responses. Read more in this issue on page 12. Original image is a primary cutaneous melanoma with little infiltration of PDCs from Fig. 1H. Artwork by Lewis Long.