Preferential homing of tumor-infiltrating lymphocytes in tumor-bearing mice.
Preferential homing of tumor-infiltrating lymphocytes in tumor-bearing mice.
复制标题
荷瘤小鼠中肿瘤浸润淋巴细胞的优先归巢。
DOI：
10.1007/bf00199283
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
McAfee,JG
中科院分区：
文献类型：
--
作者：
Ames,IH;Gagne,GM;Garcia,AM;John,PA;Scatorchia,GM;Tomar,RH;McAfee,JG
鉴于目前在晚期癌症患者过继免疫治疗中使用淋巴样细胞的兴趣，我们研究了不同淋巴效应细胞在乳腺癌荷瘤小鼠中的归巢模式。从C3H/OuJ小鼠的脾中制备了全脾细胞、自然杀伤(NK)细胞和淋巴因子激活的杀伤(LAK)细胞的单细胞悬液。肿瘤浸润性淋巴细胞(TIL)是从同一亚系的退休育种者雌性乳腺癌中分离出来的。用铟-111标记效应细胞，并通过尾静脉注射到携带一个或多个乳腺肿瘤的雌性C3H/OuJ小鼠体内。给药24小时后，总的脾细胞、NK细胞和LAK细胞均匀地分布在正常乳腺组织和乳腺癌之间。仅TIL在肿瘤组织中的浓度高于相应的正常乳腺组织。用4-H51Cr释放细胞毒试验测定不同淋巴细胞制剂对YAC-1细胞的杀伤能力。从LAK细胞培养中获得的细胞，通过不连续Percoll梯度离心法和白细胞介素2(IL-2)刺激的TIL进一步浓缩，显示出最高的细胞毒性水平，而总脾细胞和新鲜TIL的水平最低。由于IL-2刺激的TIL具有高度的细胞毒性，在肿瘤定位上优于NK细胞和LAK细胞，因此它们可能是晚期癌症过继免疫治疗的首选淋巴效应细胞。
In view of the current interest in the use of lymphoid cells in adoptive immunotherapy of patients with advanced cancer, we have studied the homing patterns of various lymphoid effector cells in mammary-tumor-bearing mice. Single-cell suspensions of total splenocytes, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were prepared from the spleens of C3H/OuJ mice. Tumor-infiltrating lymphocytes (TIL) were isolated from mammary adenocarcinomas excised from retired breeder females of the same substrain. Effector cells were labeled with indium-111 and injected via a tail vein into female C3H/OuJ mice bearing one or more mammary tumors. Twenty-four hours after administration, total splenocytes, NK cells, and LAK cells distributed themselves evenly between normal mammary tissue and mammary adenocarcinomas. Only TIL had a higher concentration in tumors than in corresponding normal mammary tissue. The ability of the different lymphocyte preparations to lyse YAC-1 cells was determined by means of a 4-h51Cr-release cytotoxicity assay. Cells harvested from LAK cell cultures and further enriched by centrifugation through a discontinuous Percoll gradient and interleukin-2 (IL-2)-stimulated TIL demonstrated the highest levels of cytotoxicity, while total splenocytes and fresh TIL were characterized by the lowest levels. Since IL-2-stimulated TIL were highly cytotoxic and exhibited better tumor localization than both NK cells and LAK cells in this system, they may be the lymphoid effectors of choice for adoptive immunotherapy of advanced cancer.