Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice.
Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice.
复制标题
DOI：
10.1007/s00262-016-1823-8
复制
发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Cho CS
中科院分区：
文献类型：
--
作者：
Contreras A;Sen S;Tatar AJ;Mahvi DA;Meyers JV;Srinand P;Suresh M;Cho CS
免疫细胞转移（ACT）黑色素瘤免疫疗法通常采用急性活化的效应CD 8 + T细胞，因为它们具有快速识别和清除抗原的能力。我们先前已经观察到效应CD 8 + T细胞对黑色素瘤诱导的抑制高度敏感，而记忆CD 8 + T细胞则不然。虽然记忆T细胞被认为是潜在的有利ACT，局部和全身的T细胞反应后效应和记忆ACT的动力学尚未进行比较。将稳定转染以表达非常低水平的淋巴细胞性脉络丛脑膜炎病毒（LCMV）肽GP 33（B16 GP 33）的B16 F10黑素瘤细胞接种到同基因C57 BL/6小鼠中。在B16 GP 33接种后1天，将相同数量的真正幼稚、效应或记忆表型GP 33特异性CD 8 + T细胞过继转移到小鼠中。ACT免疫疗法的疗效通过连续肿瘤测量和局部和全身CD 8 + T细胞应答的流式细胞术分析进行动力学评估。在记忆性CD 8 + T细胞ACT后，B16 GP 33肿瘤生长的控制、过继转移的CD 8+细胞的持续性、CD 8 + T细胞的肿瘤内浸润和系统性CD 8 + T细胞对GP 33的反应性最强。在手术肿瘤切除和黑色素瘤肿瘤攻击后，只有接受基于记忆T细胞的ACT免疫疗法的小鼠表现出持久的肿瘤特异性免疫。这些发现证明了使用非扩增的记忆性CD 8 + T细胞如何增强ACT免疫效力。
Adoptive cell transfer (ACT) melanoma immunotherapy typically employs acutely activated effector CD8+ T cells for their ability to rapidly recognize and clear antigen. We have previously observed that effector CD8+ T cells are highly susceptible to melanoma-induced suppression, whereas memory CD8+ T cells are not. Although memory T cells have been presumed to be potentially advantageous for ACT, the kinetics of local and systemic T cell responses after effector and memory ACT have not been compared. B16F10 melanoma cells stably transfected to express very low levels of the lymphocytic choriomeningitis virus (LCMV) peptide GP33 (B16GP33) were inoculated into syngeneic C57BL/6 mice. Equal numbers of bona fide naïve, effector, or memory phenotype GP33-specific CD8+ T cells were adoptively transferred into mice 1 day after B16GP33 inoculation. The efficacy of ACT immunotherapy was kinetically assessed using serial tumor measurements and flow cytometric analyses of local and systemic CD8+ T cell responses. Control of B16GP33 tumor growth, persistence of adoptively transferred CD8+ cells, intratumoral infiltration of CD8+ T cells, and systemic CD8+ T cell responsiveness to GP33 were strongest after ACT of memory CD8+ T cells. Following surgical tumor resection and melanoma tumor challenge, only mice receiving memory T cell-based ACT immunotherapy exhibited durable tumor-specific immunity. These findings demonstrate how the use of non-expanded memory CD8+ T cells may enhance ACT immunotherapeutic efficacy.