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粒细胞巨噬细胞集落刺激因子动员的外周血干细胞的抗肿瘤及辅助免疫活性

Antitumor and accessory immune activities of peripheral blood stem cells mobilized with granulocyte-macrophage colony-stimulating factor.

作者信息

Triozzi P L, Tucker F, Benzies T, Balcerzak S P

机构信息

Ohio State University Comprehensive Cancer Center, Arthur G James Cancer Hospital and Research Institute, Columbus, USA.

出版信息

Bone Marrow Transplant. 1996 Jul;18(1):47-52.

PMID:8831995
Abstract

The characteristics of PBSC mobilized with GM-CSF, which has been shown to augment monocyte/macrophage (Mo/Mx) antitumor and accessory activities, were evaluated. Patients with metastatic cancers were treated with GM-CSF at 5 micrograms/kg sc, days 1 to 7; leukaphereses were performed on days 6 and 7. A mean of 3.3 x 10(10) mononuclear cells were collected, 59% of which were lymphoid and 32%, monocytoid. Spontaneous Mo/Mx tumor cell cytotoxicity was not detectable in the leukapheresis product, either before or after cryopreservation; Mo/Mx tumor cell cytotoxicity, however, was inducible in vitro with IFN-gamma. Likewise, spontaneous lymphocyte cytotoxicity was not detectable in the leukapheresis product; lymphokine-activated killer cell activity was inducible in vitro with IL-2. Whereas lymphoproliferative responses to tetanus toxoid of cryopreserved PBSC were less than that of freshly collected PBSC, the capacity of Mo/Mx from cryopreserved PBSC to function as accessory cells in the lymphoproliferative response was maintained. These results indicate that significant numbers of immune cells can be mobilized with GM-CSF alone. Cryopreserved, GM-CSF-mobilized PBSC do not demonstrate spontaneous antitumor cytolytic activity; however, accessory activity is present and antitumor cytolytic activity mediated by both monocytoid and lymphoid cells is inducible.

摘要

对用粒细胞巨噬细胞集落刺激因子(GM-CSF)动员的外周血干细胞(PBSC)的特性进行了评估,GM-CSF已被证明可增强单核细胞/巨噬细胞(Mo/Mx)的抗肿瘤和辅助活性。转移性癌症患者在第1至7天接受皮下注射5微克/千克的GM-CSF治疗;在第6天和第7天进行白细胞分离术。平均收集到3.3×10¹⁰个单核细胞,其中59%为淋巴细胞,32%为单核样细胞。在白细胞分离产物中,无论是冷冻保存前还是冷冻保存后,均未检测到自发的Mo/Mx肿瘤细胞细胞毒性;然而,Mo/Mx肿瘤细胞细胞毒性在体外可被γ干扰素诱导。同样,在白细胞分离产物中未检测到自发的淋巴细胞细胞毒性;白细胞介素-2可在体外诱导淋巴因子激活的杀伤细胞活性。虽然冷冻保存的PBSC对破伤风类毒素的淋巴细胞增殖反应低于新鲜采集的PBSC,但冷冻保存的PBSC中Mo/Mx作为淋巴细胞增殖反应中辅助细胞的功能得以维持。这些结果表明,仅用GM-CSF就能动员大量免疫细胞。冷冻保存的GM-CSF动员的PBSC未表现出自发的抗肿瘤细胞溶解活性;然而,存在辅助活性,并且单核样细胞和淋巴细胞介导的抗肿瘤细胞溶解活性均可被诱导。

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