Memory T cells are uniquely resistant to melanoma-induced suppression.
Memory T cells are uniquely resistant to melanoma-induced suppression.
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记忆 T 细胞对黑色素瘤诱导的抑制具有独特的抵抗力。
DOI：
10.1007/s00262-012-1326-1
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Cho CS
中科院分区：
文献类型：
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作者：
Wentworth L;Meyers JV;Alam S;Russ AJ;Suresh M;Cho CS
我们先前已经观察到，体内暴露于生长的黑色素瘤肿瘤通过抑制幼稚T细胞进行抗原驱动的增殖性扩增的能力而从根本上改变了活化的T细胞的稳态。我们假设在分化后期暴露于黑色素瘤的T细胞也会有类似的抑制作用。在用淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染后8或60天，用培养基或同基因B16 F10黑素瘤肿瘤接种C57 BL/6小鼠，并且在肿瘤接种后18天使用流式细胞术定量LCMV特异性T细胞的脾群体。在感染后第8天接种黑色素瘤增强了先前激活的T细胞的收缩。这种增强的收缩与荷瘤小鼠T细胞凋亡易感性增加有关。相比之下，在感染后第60天接种黑色素瘤并不影响先前建立的记忆T细胞维持自身稳定数量的能力。此外，先前建立的记忆T细胞对LCMV攻击的反应能力不受黑素瘤的影响。过继转移到黑色素瘤荷瘤小鼠后，肿瘤特异性记忆T细胞在控制黑色素瘤生长方面比同等数量的肿瘤特异性效应T细胞显着更有效。这些观察结果表明，记忆T细胞对黑色素瘤对激活的T细胞稳态的抑制性影响具有独特的抵抗力;这些发现可能对基于T细胞的癌症免疫疗法产生影响。
We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell–based cancer immunotherapy.