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.
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.
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DOI：
10.1016/j.neo.2016.02.006
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Tanaka J
中科院分区：
文献类型：
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作者：
Kobayashi K;Yano H;Umakoshi A;Matsumoto S;Mise A;Funahashi Y;Ueno Y;Kamei Y;Takada Y;Kumon Y;Ohnishi T;Tanaka J
CD200在表达其受体CD200R的骨髓细胞中诱导免疫抑制，这可能对肿瘤免疫产生影响。我们发现，人癌组织不仅表达全长CD200 (CD200L)，也表达其截短形式CD200S。尽管有报道称CD200S可以拮抗CD200L的免疫抑制作用，但CD200S在肿瘤免疫中的作用从未被研究过。我们建立了表达CD200L或CD200S的大鼠C6胶质瘤细胞系；原C6细胞系不表达CD200分子。细胞系的生长无明显差异。移植到新生Wistar大鼠前脑实质后，移植C6- cd200s细胞的大鼠存活时间明显长于移植原C6和C6- cd200l细胞的大鼠。C6-CD200S肿瘤比C6-CD200L或c6原肿瘤体积小，肿瘤细胞聚集体中存在大量凋亡细胞。肿瘤相关巨噬细胞（tam）在C6-CD200S肿瘤中表现为树突状细胞（DC）样形态，具有多过程和CD86表达。CD3+、CD4+、CD8+细胞在C6-CD200S肿瘤中多见，DC标志物、颗粒酶、穿孔素在C6-CD200S肿瘤中表达增加。从原始C6肿瘤中分离的tam与C6- cd200s细胞共培养，显示DC标记物的表达增加。这些结果表明，CD200S激活tam成为dc样抗原提呈细胞，导致CD8+细胞毒性T淋巴细胞的激活，从而诱导肿瘤细胞的凋亡消除。CD200S作用的研究结果可能为肿瘤的治疗提供一种新的治疗方式。
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.