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前房相关免疫偏离促进小鼠同基因眼内肿瘤生长

Promotion of syngeneic intraocular tumor growth in mice by anterior chamber-associated immune deviation.

作者信息

Niederkorn J Y, Streilein J W, Kripke M L

出版信息

J Natl Cancer Inst. 1983 Jul;71(1):193-9.

PMID:6575203
Abstract

Regressor tumors (P91 and UV-5C25), known to express potent tumor-specific transplantation antigens, were briskly rejected when transplanted either sc or ip into syngeneic mice (DBA/2 and BALB/c, respectively). These tumors demonstrated markedly different behavior following transplantation into the anterior chamber of syngeneic mice. Tumors grew to significant masses and survived for prolonged periods within the anterior chamber of the eye. The extended growth and survival of regressor tumors in the anterior chamber (i.e. immune privilege) were abrogated by splenectomy and thus resemble anterior chamber-associated immune deviation. However, this immune privilege proved to be temporary and was superseded by complete tumor resolution. Studies of mice immunosuppressed with UV light or X-ray irradiation demonstrated that spontaneous intraocular resolution of regressor tumors was due to specific systemic immunity that not only led to intraocular tumor resolution but also prevented the spread of the primary intraocular tumor to distant organs and rendered the hosts highly resistant to secondary challenge with sc tumor inocula. The present findings were relevant to understanding human retinoblastoma, an intraocular neoplasm demonstrating a high incidence of spontaneous resolution, and will hopefully form a foundation for designing, immunotherapeutic strategies for treating human intraocular neoplasms.

摘要

已知表达强效肿瘤特异性移植抗原的回归性肿瘤(P91和UV - 5C25),当分别皮下或腹腔内移植到同基因小鼠(分别为DBA/2和BALB/c)体内时,会迅速被排斥。这些肿瘤在移植到同基因小鼠的前房后表现出明显不同的行为。肿瘤在前房内生长到相当大的体积并存活较长时间。回归性肿瘤在前房内的延长生长和存活(即免疫赦免)通过脾切除术被消除,因此类似于前房相关免疫偏离。然而,这种免疫赦免被证明是暂时的,随后被肿瘤完全消退所取代。对用紫外线或X射线照射进行免疫抑制的小鼠的研究表明,回归性肿瘤的自发性眼内消退是由于特异性全身免疫,这种免疫不仅导致眼内肿瘤消退,还能防止原发性眼内肿瘤扩散到远处器官,并使宿主对皮下肿瘤接种的二次攻击具有高度抗性。本研究结果与理解人类视网膜母细胞瘤相关,视网膜母细胞瘤是一种眼内肿瘤,具有很高的自发性消退发生率,有望为设计治疗人类眼内肿瘤的免疫治疗策略奠定基础。

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