Given the striking similarity between TSC tumors and melanoma, such as high expression of melanocyte genes CTSK and MITF and similar tumor microenvironment crosstalk revealed by this study, the regulatory axis from SLS tumor cells to T-cell dysfunction via TREM2+/TYROBP+ M2-like macrophages identified in this study might be a conserved mechanism across tumor types. Here, TYROBP is linked to tuberous sclerosis.