Harlin H, Artz A S, Mahowald M, Rini B I, Zimmerman T, Vogelzang N J, Gajewski T F
Department of Pathology, The University of Chicago, IL 60637, USA.
Bone Marrow Transplant. 2004 Mar;33(5):491-7. doi: 10.1038/sj.bmt.1704385.
Nonmyeloablative allogeneic stem cell transplantation (NST) is thought to be an immunologic therapy in which donor T cells mediate a graft-versus-tumor effect. We recently reported the clinical outcome of a phase II trial of NST in metastatic renal cell carcinoma (RCC). However, the immune response correlates of clinical activity remain unknown. We now describe the analysis of T-cell subsets and T-cell cytokine-producing potential for those patients evaluable for immune monitoring. The incidence of graft-versus-host disease (GVHD) correlated with clinical outcome, with all responders exhibiting chronic GVHD. Following initial tapering of immunosuppression, an increase in the total numbers of CD8+ T cells but not CD4+ T cells was observed among responders compared to nonresponders. In addition, a greater ratio of CD8+ to CD4+ T cells producing IFN-gamma and IL-2 was seen in clinical responders at the time when clinical responses were first detected (day 180 after transplantation). Our results support the hypothesis that the antitumor effects of NST may be mediated by IFN-gamma-producing CD8+ T cells, and indicate that isolation of putative tumor antigen-specific T cells, ideally, should be pursued around day +180.
非清髓性异基因干细胞移植（NST）被认为是一种免疫治疗方法，其中供体T细胞介导移植物抗肿瘤效应。我们最近报告了NST治疗转移性肾细胞癌（RCC）的II期试验的临床结果。然而，临床活性的免疫反应相关性仍然未知。我们现在描述了对那些可进行免疫监测的患者的T细胞亚群和T细胞产生细胞因子潜力的分析。移植物抗宿主病（GVHD）的发生率与临床结果相关，所有反应者均表现出慢性GVHD。在最初逐渐减少免疫抑制后，与无反应者相比，反应者中观察到CD8 + T细胞总数增加，但CD4 + T细胞未增加。此外，在首次检测到临床反应时（移植后第180天），临床反应者中产生IFN-γ和IL-2的CD8 +与CD4 + T细胞的比例更高。我们的结果支持以下假设，即NST的抗肿瘤作用可能由产生IFN-γ的CD8 + T细胞介导，并表明理想情况下，应在+180天左右分离假定的肿瘤抗原特异性T细胞。
