title: Apoptotic Melanoma B16-F1 Cells Induced by Lidamycin Could Initiate the Antitumor Immune Response in BABL/c Mice.
abstract: In the process of tumor cell apoptosis induced by specific regents, calreticulin (CRT) was transferred from endoplasmic reticulum (ER) onto the cell membrane. These tumor cells, when used as the cellular vaccine to immunize experimental animals, could initiate effective antitumor immunoresponse against homologous tumor cells. This is referred to as immunogenic cell death. Lidamycin (LDM) is an enediyne antibiotic, which has extremely potent cytotoxicity to cancer cells. In this study, the mouse melanoma B16-F1 cancer cells were used to investigate the ability of LDM in promoting immunogenic cell death. Our data showed that LDM could induce apoptosis of B16-F1 cancer cells, accompanied by CRT translocation onto the cell membrane. These LDM-treated B16-F1 cells could be recognized and phagocytosed more efficiently by macrophage and dendritic cells. When the LDM-treated apoptotic B16-F1 cells were used as a whole-cell tumor vaccine to immune mice, the mice obtained resistance against rechallenged B16-F1 living cells. At the same time, the specific antitumor immune response was observed in these vaccinated mice. The splenocytes from the mice vaccinated with LDM-treated B16-F1 cells showed significantly enhanced NK lymphocyte activities and also faster growth rate and increased secretion of IFN-γ when encountering the cellular antigens from B16-F1 cells. All these results suggested that LDM could promote immunogenic cell death in B16-F1 cells, and these LDM-treated B16-F1 cells could be used as a sort of cell vaccine to initiate effective antitumor immunoresponse in mice.
authors.affiliation: China Three Gorges University Medical College, Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, Yichang, Hubei, China.
authors.forename: Jian-lin
authors.initials: JL
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Qin
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Chu-yu
authors.initials: CY
authors.lastname: Cao
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Ya-feng
authors.initials: YF
authors.lastname: Lv
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D064032:Calbindin 2 / Q000378:metabolism; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D004354:Drug Screening Assays, Antitumor; D053281:Enediynes / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010587:Phagocytosis
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; C576511:Calb2 protein, mouse; D064032:Calbindin 2; D053281:Enediynes; C058024:C 1027