Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers
Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers
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DOI：
10.1038/s41591-018-0266-5
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发表时间：
2019-01-01
期刊：
影响因子：
82.9
通讯作者：
Schumacher, Ton N.
中科院分区：
文献类型：
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作者：
Scheper, Wouter;Kelderman, Sander;Schumacher, Ton N.
T细胞对人类癌症的浸润通常被解释为免疫识别的标志，并且越来越多的努力重新激活这些肿瘤部位的功能失调的T细胞（1）。然而，这些努力只有在这些细胞的肿瘤内T细胞受体（TCR）库本质上是肿瘤反应性的情况下才有价值，并且这对于大多数人类癌症还没有以无偏见的方式建立。为了解决这个问题，我们分析了卵巢癌和结直肠癌中CD8（+）T细胞的肿瘤内TCR库的内在肿瘤反应性，这两种肿瘤类型的T细胞浸润形成了阳性预后标志物（2，3）。获得的数据表明，识别自体肿瘤的能力仅限于约10%的肿瘤内CD8（+）T细胞。此外，在测试的四个患者样品中的两个中，尽管T细胞浸润了他们的肿瘤，但没有鉴定出肿瘤反应性TCR。这些数据表明，肿瘤内T细胞识别邻近肿瘤组织的内在能力可能是罕见的和可变的，并表明重新激活肿瘤内T细胞的临床努力将受益于同时提高肿瘤内TCR库质量的方法。
Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites(1). However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor reactivity of the intratumoral TCR repertoire of CD8(+) T cells in ovarian and colorectal cancer-two tumor types for which T cell infiltrates form a positive prognostic marker(2,3). Data obtained demonstrate that a capacity to recognize autologous tumor is limited to approximately 10% of intratumoral CD8(+) T cells. Furthermore, in two of four patient samples tested, no tumor-reactive TCRs were identified, despite infiltration of their tumors by T cells. These data indicate that the intrinsic capacity of intratumoral T cells to recognize adjacent tumor tissue can be rare and variable, and suggest that clinical efforts to reactivate intratumoral T cells will benefit from approaches that simultaneously increase the quality of the intratumoral TCR repertoire.