We have developed nanoparticle-mediated TRPV1 blockade as a highly effective approach to modulate nuclear translocation of HSF1, which selectively suppresses HSP and TGFβ self-defense pathways in tumors for achieving potent thermo-immunotherapy against highly malignant tumors such as intractable pancreatic cancers. Here, TRPV1 is linked to familial pancreatic carcinoma.