Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses
Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses
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DOI：
10.1182/blood.v100.5.1551.h81702001551_1551_1558
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发表时间：
2002-09-01
期刊：
影响因子：
20.3
通讯作者：
Leonard, JP
中科院分区：
文献类型：
--
作者：
Dunussi-Joannopoulos, K;Zuberek, K;Leonard, JP
趋化因子基质细胞衍生因子I（SDF-1）是围产期存活、B淋巴细胞生成和骨髓骨髓生成所必需的，并且是有效的单核细胞和T淋巴细胞化学引诱物。SDF-1与其受体CXCR 4的相互作用与CD 34（+）细胞迁移和归巢有关。这里显示，由hSDF-1 β转导的肿瘤细胞单独分泌的人SDF-1 β（hSDF-1 β）促进有效的抗肿瘤应答。研究了小鼠C1498白血病和B16 F1黑色素瘤模型。为了通过肿瘤细胞（SDF-肿瘤细胞）表达hSDF-1 β 0，已经使用了分泌编码hSDF-1 β的逆转录病毒的包装细胞系。结果表明，50%（B16 F1）和90%（C1498）的注射SDF-肿瘤细胞的幼稚小鼠排斥它们的肿瘤。用经照射的SDF-肿瘤细胞对幼稚小鼠进行预防性疫苗接种导致全身免疫，并且治疗性疫苗接种导致已建立的肿瘤的治愈。先前排斥活SDF肿瘤细胞的小鼠对被排斥的肿瘤具有免疫力，但对另一种肿瘤易感，并具有体外肿瘤特异性细胞毒性T淋巴细胞（CTL）活性。SDF-肿瘤细胞不被免疫缺陷的scid小鼠排斥。免疫组织化学显示T细胞显著浸润SDF-1肿瘤，体内T细胞耗竭研究表明SDF介导的肿瘤排斥反应需要CD 4（+）T细胞。总之，目前的数据表明，SDF-1/CXCR 4的相互作用有可能调节有效的抗肿瘤免疫反应，这些相互作用的开发可能会导致新的治疗干预措施。(C)2002年，美国血液学会。
The chemokine stromal cell-derived factor I (SDF-1) is essential for perinatal viability, B lymphopoiesis, and bone marrow myelopoiesis, and is a potent monocyte and T-lymphocyte chemoattractant. Interactions of: SDF-1 with its receptor CXCR4 have been implicated in CD34(+) cell migration and homing. Here it is shown that human SDF-1beta (hSDF-1beta) alone secreted by hSDF-1beta-transduced tumor cells promotes efficacious antitumor responses. The murine C1498 leukemia and B16F1 melanoma models have been studied. For expression of hSDF-1beta 0 by tumor cells (SDF-tumor cells), packaging cell lines secreting retroviruses encoding hSDF-1beta have been used. The results demonstrate that 50% (B16F1) and 90% (C1498) of naive mice injected with SDF-tumor cells reject their tumors. Prophylactic vaccination of naive mice with irradiated SDF-tumor cells leads to systemic immunity, and therapeutic vaccination leads to cure of established tumors. Mice that previously rejected live SDF-tumor cells are immune to the rejected tumor but susceptible to another tumor and have in vitro tumor-specific cytotoxic T lymphocyte (CTL) activity. SDF-tumor cells are not rejected by immunodeficient scid mice. Immunohistochemistry shows significant infiltration of SDF-1 tumors by T cells, and in vivo T-cell depletion studies indicate that CD4(+) T cells are required for SDF-mediated tumor rejection. In conclusion, the present data suggest that SDF-1/CXCR4 interactions have the potential to regulate efficacious antitumor immune responses; exploitation of these interactions may lead to novel therapeutic interventions. (C) 2002 by The American Society of Hematology.