Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas
Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas
复制标题
DOI：
10.1182/blood-2002-01-0174
复制
发表时间：
2002-08-15
期刊：
影响因子：
20.3
通讯作者：
Jadus, MR
中科院分区：
文献类型：
--
作者：
Chen, YJ;Douglass, T;Jadus, MR
用膜巨噬细胞集落刺激因子（mM-CSF）转染的克隆T9-C2胶质瘤细胞在植入Fischer大鼠皮下时从未形成肿瘤，而对照T9细胞则形成了肿瘤。T9-C2细胞在1天内通过类似于侧下垂的机制被完全杀死。T9-C2细胞的线粒体和内质网在植入后4小时内开始酸化。到24小时，死亡的肿瘤细胞肿胀，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性。Bcl-2转导的T9-C2细胞在大鼠中不能形成肿瘤。T9和T9-C2细胞都产生了奎宁诱导的中性粒细胞化学引诱物，该化学引诱物将粒细胞募集到肿瘤注射部位，在那里它们与肿瘤细胞相互作用。新鲜分离的巨噬细胞在体外通过独立于吞噬作用的机制杀死T9-C2细胞。用抗去唾液酸GM 1抗体处理的无胸腺裸大鼠形成T9-C2肿瘤，而用自然杀伤细胞（NK）特异性抗体处理的大鼠未能形成肿瘤。当用抗多形核白细胞（抗PMN）和抗巨噬细胞抗体治疗时，80%的裸鼠形成肿瘤，而当使用单一抗体时，只有40%的大鼠形成肿瘤。这表明PMN和巨噬细胞都参与了T9-C2肿瘤细胞的杀伤。免疫功能正常的大鼠对T9细胞颅内再攻击有免疫反应。如果在注射前将T9-C2细胞冻融、X射线照射或用丝裂霉素-C处理，则不会发生接种效应。使用mM-CSF转导的T9细胞的最佳肿瘤免疫需要活的肿瘤细胞。在这项研究中，当在注射肿瘤细胞时诱导强烈的炎症反应时，发生最佳的肿瘤免疫。(C)2002年，美国血液学会。
Cloned T9-C2 glioma cells transfected with membrane macr6phage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C2 cell's mitochondria and endoplasmic reticulum started within 4 hours after implantation. By 24 hours, the dead tumor cells were swollen and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)positive. Bcl2-transduced T9-C2 cells failed to form tumors in rats. Both T9 and T9-C2 cells produced cytokine-induced neutrophil chemoattractant that recruited the granulocytes into the tumor injection sites, where they interacted with the tumor cells. Freshly isolated macrophages killed the T9-C2 cells in vitro by a mechanism independent of phagocytosis. Nude athymic rats treated with antiasialo GM1 antibody formed T9-C2 tumors, whereas rats treated with a natural killer cell (NK)-specific antibody failed to form tumors. When treated with antipolymorphonuclear leukocyte (anti-PMN) and antimacrophage antibodies, 80% of nude rats formed tumors, whereas only 40% of the rats developed 6 tumor when a single antibody was used. This suggests that both PMNs and macrophages are involved in the killing of T9-C2 tumor cells. Immunocompetent rats that rejected the living T9-C2 cells Were immune to the intracranial rechallenge with T9 cells. No vaccinating effect occurred if the T9-C2 cells were freeze-thawed, x-irradiated, or treated with mitomycin-C prior to injection. Optimal tumor immunization using mM-CSF-transduced T9 cells requires viable tumor cells. In this study optimal tumor immunization occurred when a strong inflammatory response at the injection of the tumor cells was induced. (C) 2002 by The American Society of Hematology.