Symons Heather J, Levy Moshe Y, Wang Jie, Zhou Xiaotao, Zhou Gang, Cohen Sarah E, Luznik Leo, Levitsky Hyam I, Fuchs Ephraim J
Division of Cancer Immunology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
Biol Blood Marrow Transplant. 2008 May;14(5):499-509. doi: 10.1016/j.bbmt.2008.02.013.
The "allogeneic effect" refers to the induction of host B cell antibody synthesis or host T cell cytotoxicity, including tumoricidal activity, by an infusion of allogeneic lymphocytes. We show that treatment of mice with cyclophosphamide (Cy) followed by CD8(+) T cell-depleted allogeneic donor lymphocyte infusion (Cy + CD8(-) DLI) induces regression of established tumors with minimal toxicity in models of both hematologic and solid cancers, even though the donor cells are eventually rejected by the host immune system. The optimal antitumor effect of Cy + CD8(-) DLI required the presence of donor CD4(+) T cells, host CD8(+) T cells, and alloantigen expression by normal host but not tumor tissue. The results support a model in which a donor CD4(+) T cell-mediated graft-versus-host (GVH) reaction effectively awakens antitumor immunity among Cy-resistant host CD8(+) T cells. These events provide the cellular mechanism of the "allogeneic effect" in antitumor immunity. Cy + CD8(-) DLI may be an effective and minimally toxic strategy for awakening the host immune response to advanced cancers.
“同种异体效应”是指通过输注同种异体淋巴细胞诱导宿主B细胞抗体合成或宿主T细胞细胞毒性，包括杀肿瘤活性。我们发现，在血液系统癌症和实体癌模型中，用环磷酰胺（Cy）治疗小鼠后，再输注去除CD8(+) T细胞的同种异体供体淋巴细胞（Cy + CD8(-) DLI），可诱导已形成肿瘤的消退，且毒性最小，尽管供体细胞最终会被宿主免疫系统排斥。Cy + CD8(-) DLI的最佳抗肿瘤效果需要供体CD4(+) T细胞、宿主CD8(+) T细胞的存在，以及正常宿主而非肿瘤组织表达同种异体抗原。这些结果支持了一种模型，即供体CD4(+) T细胞介导的移植物抗宿主（GVH）反应有效地唤醒了Cy抗性宿主CD8(+) T细胞中的抗肿瘤免疫。这些事件提供了抗肿瘤免疫中“同种异体效应”的细胞机制。Cy + CD8(-) DLI可能是一种有效且毒性最小的策略，用于唤醒宿主对晚期癌症的免疫反应。
