The Th1 response induces epitope spreading to prevent tumor relapse due to antigen escape (60).This study highlighted that cryo-thermal Th1-dominant CD4+ T cells improved CTL generation as well as APC maturation to augment antitumor responses in the replacement of typical maturation reagents in vitro, and adoptively transferred cryo-thermal CD4+ T cells significantly decreased the growth of tumors in vivo, which suggest that cryo-thermal therapy could be further developed as a thermo-immunotherapy for clinical application. Here, CD4 is linked to neoplasm.