T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells
T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells
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DOI：
10.1073/pnas.202491499
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发表时间：
2002-10-01
影响因子：
11.1
通讯作者：
Olson, K
中科院分区：
文献类型：
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作者：
Dhodapkar, MV;Krasovsky, J;Olson, K
大多数未经治疗的癌症患者会发展为进展性肿瘤。我们测试了来自临床进展性多发性骨髓瘤患者的T淋巴细胞对新鲜自体肿瘤发展杀伤功能的能力。在这种恶性肿瘤中，重复性地评估新鲜分离的肿瘤细胞和从骨髓肿瘤环境中分离的T细胞是可行的。当我们对连续七名患者进行这项研究时，所有临床阶段的患者都没有检测到对自体癌细胞的反应。然而，在7名患者中，有6名患者在体外用处理过自体肿瘤细胞的树突状细胞刺激后，对自体骨髓瘤产生了溶细胞和产生干扰素-γ的反应。抗肿瘤效应识别新鲜的自体肿瘤，但不识别骨髓中的非肿瘤细胞、骨髓瘤细胞系、负载肿瘤来源Ig的树突状细胞或同种异体肿瘤。重要的是，这些CD8(+)效应器通过使用血液和骨髓肿瘤环境中的T细胞产生了类似的效率。因此，即使在临床肿瘤进展的背景下，骨髓瘤患者的肿瘤床上也含有T细胞，这些T细胞可以很容易地被树突状细胞激活以杀死原发的自体肿瘤。
Most untreated cancer patients develop progressive tumors. We tested the capacity of T lymphocytes from patients with clinically progressive, multiple myeloma to develop killer function against fresh autologous tumor. In this malignancy, it is feasible to reproducibly evaluate freshly isolated tumor cells and T cells from the marrow tumor environment. When we did this with seven consecutive patients, with all clinical stages of disease, we did not detect reactivity to autologous cancer cells. However, both cytolytic and IFN-gamma-producing responses to autologous myeloma were generated in six of seven patients after stimulation ex vivo with dendritic cells that had processed autologous tumor cells. The antitumor effectors recognized fresh autologous tumor but not nontumor cells in the bone marrow, myeloma cell lines, dendritic cells loaded with tumor-derived Ig, or allogeneic tumor. Importantly, these CD8(+) effectors developed with similar efficiency by using T cells from both the blood and the bone marrow tumor environment. Therefore, even in the setting of clinical tumor progression, the tumor bed of myeloma patients contains T cells that can be activated readily by dendritic cells to kill primary autologous tumor.