Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy
Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy
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DOI：
10.1182/blood.v99.9.3280
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发表时间：
2002-05-01
期刊：
影响因子：
20.3
通讯作者：
Yi, Q
中科院分区：
文献类型：
--
作者：
Wen, YJ;Min, R;Yi, Q
由骨髓瘤浆细胞分泌的独特型蛋白是肿瘤特异性但弱的抗原。在骨髓瘤患者中探索了基于特发性的免疫治疗，结果令人失望。可以想象，骨髓瘤细胞含有多种肿瘤抗原，可以更有效地刺激抗肿瘤T细胞。为了探索利用骨髓瘤细胞作为肿瘤抗原来源进行免疫治疗的可能性，本研究采用骨髓瘤细胞裂解物致敏的树突状细胞（DCs）作为刺激细胞，制备骨髓瘤特异性细胞毒性T淋巴细胞（CTL）并检测其功能。在重复刺激后，从骨髓瘤患者中产生含有CD 4（+）和CD 8（+）T细胞的特异性CTL细胞系。我们的研究结果表明，这些T细胞不仅识别和裂解自体骨髓瘤蛋白脉冲的DC，他们也杀死自体原代骨髓瘤细胞。偶尔，CTL对自体独特型脉冲DC和同种异体原代骨髓瘤细胞有反应。然而，未检测到针对自体淋巴细胞（包括B细胞）的细胞溶解活性，表明T细胞特异性地针对骨髓瘤细胞起作用。对靶细胞的细胞毒性是主要组织相容性复合物I类，在较小程度上，2类限制，主要依赖于穿孔素介导的途径。CTL在抗原刺激下主要分泌干扰素-γ和肿瘤坏死因子-α，指示1型T细胞亚群。这些发现首次证明了肿瘤细胞裂解物引发的CTL仅杀死骨髓瘤细胞，而不是自体淋巴细胞。这为多发性骨髓瘤中基于骨髓瘤细胞的免疫治疗提供了理论基础。(C)2002年，美国血液学会。
The Idiotype protein, secreted by myeloma plasma cells, Is a tumor-specific but weak antigen. Idiotype-based Immunotherapy has been explored In myeloma patients with disappointing results. It is conceivable that myeloma cells contain a multitude of tumor antigens that can more effectively stimulate antitumor T cells. To explore the possibility of using whole myeloma cells as a source of tumor antigens for Immunotherapy, the current study was undertaken to generate and examine the function of myeloma-specific cytotoxic T lymphocytes (CTLs) by using dendritic cells (DCs) pulsed with myeloma cell lysates as stimulating cells. After repeated stimulation, specific CTL lines, containing CD4(+) and CD8(+) T cells, were generated from myeloma patients. Our results show that these T cells not only recognized and lysed autologous myeloma protein-pulsed DCs, they also killed autologous primary myeloma cells. Occasionally, CTLs responded to autologous idiotype-pulsed DCs and to allogeneic primary myeloma cells. No cytolytic activity, however, was detected against autologous lymphocytes including B cells, suggesting that the T cells acted specifically against myeloma cells. Cytotoxicity against target cells was major histocompatibility complex class I and, to a lesser extent, class 2 restricted and was dependent mainly on the perforin-mediated pathway. CTLs secreted predominantly interferon-gamma and tumor necrosis factor-alpha on antigenic stimulation, Indicating a type 1 T-cell subset. These findings represent the first demonstration that tumor cell lysate-primed CTLs kill only myeloma cells, not autologous lymphocytes. This provides a rationale for myeloma cell-based Immunotherapy In multiple myelome. (C) 2002 by The American Society of Hematology.