In summary, we reported the xbp1/hsp70-driven TRP2 genetic skin immunization effectively promotes durable antitumor immunity against PD1 (and Brafi)-resistant, multifocal melanoma and that this treatment sensitizes PD1-resistant disease to corollary (re)treatment with αPD1 mAb-based immunotherapy. This evidence concerns the gene XBP1 and melanoma.