Sawamura Y
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1991 Nov;66(6):868-78.
The present study was conducted in order to examine the feasibility of isolating and growing glioma-infiltrating lymphocytes in vitro as possible effector cells for use in an adoptive immunotherapy. Thirty surgical specimens obtained from patients with malignant astrocytomas were studied. The glioma-infiltrating lymphocytes were separated from tumor tissue, expanded in the presence of interleukin-2, and evaluated their anti-tumor activities in vitro. Eighteen of 30 cultures of glioma-derived lymphocytes expanded with a substantial increase in cell numbers, of at least 5 x 10(8) cells up to 5 x 10(9), 4 to 8 weeks after the initiation of culture. The expanding glioma-derived lymphocytes consisted of 88 +/- 10% CD3+ T cells including both CD4+ and CD8+ subpopulations. CD16 was expressed on 4 +/- 5% of the cells and three cultures studied exhibited 14% +/- 1 of CD56+ cells. After 4 to 8 weeks of the proliferation period, the lymphocytes ceased to grow in all cultures. The glioma-derived effector lymphocytes could lyse almost all the autologous tumor targets as well as allogeneic glioma cells. The cytotoxic activity of the glioma-derived lymphocytes appeared to be similar or inferior to that of interleukin-2-activated peripheral blood lymphocytes obtained from the same patients in killing autologous glioma cells. The glioma-derived effector cells could also lyse three-dimensional glioma targets (spheroids), but this lytis activity was clearly lower than that of the activated peripheral blood lymphocytes. Ability of these effector cells to infiltrate glioma tissue was doubtful, since after 24-hours coculture of effector cells with target spheroids, the effector cells scarcely infiltrated the spheroids. In summary, glioma-derived lymphocytes expanded in bulk culture with interleukin-2 consisted predominantly of T-lymphoblasts with the ability to kill autologous glioma cells and also to lyse glioma spheroids. However a benefit of use of the glioma-derived lymphocyte as a novel effector cells in clinical trail replacing the IL-2-activated peripheral blood lymphocytes could not be found.
本研究旨在探讨体外分离和培养胶质瘤浸润淋巴细胞作为过继性免疫治疗中可能的效应细胞的可行性。研究了30例恶性星形细胞瘤患者的手术标本。从肿瘤组织中分离出胶质瘤浸润淋巴细胞，在白细胞介素-2存在的情况下进行扩增，并在体外评估其抗肿瘤活性。30个胶质瘤来源淋巴细胞培养物中有18个在培养开始后4至8周细胞数量大幅增加，至少从5×10⁸个细胞增加到5×10⁹个细胞。扩增的胶质瘤来源淋巴细胞由88±10%的CD3⁺T细胞组成，包括CD4⁺和CD8⁺亚群。4±5%的细胞表达CD16，所研究的三个培养物中有14%±1%的细胞表达CD56⁺。在增殖期4至8周后，所有培养物中的淋巴细胞均停止生长。胶质瘤来源的效应淋巴细胞几乎可以裂解所有自体肿瘤靶标以及同种异体胶质瘤细胞。在杀伤自体胶质瘤细胞方面，胶质瘤来源淋巴细胞的细胞毒性活性似乎与从同一患者获得的白细胞介素-2激活的外周血淋巴细胞相似或更低。胶质瘤来源的效应细胞也可以裂解三维胶质瘤靶标（球体），但这种裂解活性明显低于激活的外周血淋巴细胞。这些效应细胞浸润胶质瘤组织的能力令人怀疑，因为效应细胞与靶标球体共培养24小时后，效应细胞几乎没有浸润球体。总之，用白细胞介素-2在大量培养中扩增的胶质瘤来源淋巴细胞主要由具有杀伤自体胶质瘤细胞和裂解胶质瘤球体能力的T淋巴母细胞组成。然而，未发现将胶质瘤来源淋巴细胞作为新型效应细胞用于临床试验以替代白细胞介素-2激活的外周血淋巴细胞的益处。
