A Truncated form of CD200 (CD200S) Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages.
CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L) but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs) in C6-CD200S tumors displayed dendritic cell (DC)-like morphology with multiple processes and CD86 expression. Furthermore, CD3(+), CD4(+) or CD8(+) cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8(+) cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas.
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan; Department of Hepato-biliary pancreatic surgery and breast surgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Kana
K
Kobayashi
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Hajime
H
Yano
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Akihiro
A
Umakoshi
Department of Regeneration of Community Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Shirabe
S
Matsumoto
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Ayano
A
Mise
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yu
Y
Funahashi
Department of Hepato-biliary pancreatic surgery and breast surgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yoshitomo
Y
Ueno
Department of Hepato-biliary pancreatic surgery and breast surgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yoshiaki
Y
Kamei
Department of Hepato-biliary pancreatic surgery and breast surgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yasutsugu
Y
Takada
Department of Regeneration of Community Medicine, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Yoshiaki
Y
Kumon
Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Takanori
T
Ohnishi
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan. Electronic address: jtanaka@m.ehime-u.ac.jp.
Junya
J
Tanaka
D017398:Alternative Splicing; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D015415:Biomarkers; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D059016:Tumor Microenvironment
D015703:Antigens, CD; D015415:Biomarkers; D012333:RNA, Messenger; C042739:antigens, CD200