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 sites¹. 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.

中文翻译：

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肿瘤内 TCR 库在人类癌症中的低和可变的肿瘤反应性。

T 细胞对人类癌症的浸润通常被解释为免疫识别的标志，并且在这些肿瘤部位¹重新激活功能失调的 T 细胞的努力越来越多。然而，只有当此类细胞的肿瘤内 T 细胞受体 (TCR) 库本质上具有肿瘤反应性时，这些努力才有价值，并且对于大多数人类癌症还没有以公正的方式确定这一点。^{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- T 细胞浸润形成阳性预后标志物的两种肿瘤类型^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本中，有两个没有发现肿瘤反应性 TCR，尽管 T 细胞浸润了肿瘤。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且可变的，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。