Immunological factors relating to the antitumor effect of temozolomide chemoimmunotherapy in a murine glioma model.
In this study, we investigated the potential of combined treatment with temozolomide (TMZ) chemotherapy and tumor antigen-pulsed dendritic cells (DCs) and the underlying immunological factors of TMZ chemoimmunotherapy with an intracranial GL26 glioma animal model. The combined treatment enhanced the tumor-specific immune responses and prolonged the survival more effectively than either single therapy in GL26 tumor-bearing animals. Apoptosis was induced in the tumors of the animals by the treatment with TMZ. Calreticulin (CRT) surface exposure was detected by immunofluorescence staining of TMZ-treated GL26 cells. TMZ chemotherapy increased tumor antigen cross-priming from tumor cells, leading to cross-priming of tumor antigen-specific CD4(+) T cells and CD8(+) T cells. This chemotherapy appeared to suppress the frequency of CD4(+) CD25(+) regulatory T cells (Treg). Moreover, this combined therapy resulted in an increase in the tumor infiltration of CD4(+) and CD8(+) T cells. Collectively, the findings of this study provide evidence that the combination of TMZ chemotherapy and treatment with DC-based vaccines leads to the enhancement of antitumor immunity through increased tumor-specific immune responses via the cross-priming of apoptotic tumor cell death mediated by CRT exposure and, in part, the suppression of Treg. Therefore, CRT exposure, regulatory T cells, and cross-priming by TMZ chemotherapy may be immunological factors related to the enhancement of the antitumor effects of chemoimmunotherapy in an experimental brain tumor model.
Kim
Tai-Gyu
TG
Department of Neurosurgery, Kangnam St Mary's Hospital, The Catholic University of Korea, Banpo-dong 505, Seochogu, Seoul 137-701, South Korea.
Kim
Chang-Hyun
CH
Park
Jung-Sun
JS
Park
Sung-Dong
SD
Kim
Chung Kwon
CK
Chung
Dong-Sup
DS
Hong
Yong-Kil
YK
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000077204:Temozolomide
D000970:Antineoplastic Agents; D003606:Dacarbazine; D000077204:Temozolomide