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CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor
Immunity ( IF 25.5 ) Pub Date : 2022-12-28 , DOI: 10.1016/j.immuni.2022.12.002 Nataliya Prokhnevska 1 , Maria A Cardenas 1 , Rajesh M Valanparambil 2 , Ewelina Sobierajska 1 , Benjamin G Barwick 3 , Caroline Jansen 4 , Adriana Reyes Moon 1 , Petra Gregorova 1 , Luke delBalzo 1 , Rachel Greenwald 1 , Mehmet Asim Bilen 3 , Mehrdad Alemozaffar 4 , Shreyas Joshi 4 , Cara Cimmino 4 , Christian Larsen 5 , Viraj Master 4 , Martin Sanda 4 , Haydn Kissick 6
Immunity ( IF 25.5 ) Pub Date : 2022-12-28 , DOI: 10.1016/j.immuni.2022.12.002 Nataliya Prokhnevska 1 , Maria A Cardenas 1 , Rajesh M Valanparambil 2 , Ewelina Sobierajska 1 , Benjamin G Barwick 3 , Caroline Jansen 4 , Adriana Reyes Moon 1 , Petra Gregorova 1 , Luke delBalzo 1 , Rachel Greenwald 1 , Mehmet Asim Bilen 3 , Mehrdad Alemozaffar 4 , Shreyas Joshi 4 , Cara Cimmino 4 , Christian Larsen 5 , Viraj Master 4 , Martin Sanda 4 , Haydn Kissick 6
Affiliation
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Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8 T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1 stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8 T cells. Murine tumor models revealed that tumor-specific CD8 T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8 T cell activation in response to cancer is different from that of canonical CD8 T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8 T cell activation: initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation.
中文翻译：
癌症中 CD8+ T 细胞的激活包括淋巴结中的初始激活阶段，随后是肿瘤内的效应细胞分化
肿瘤免疫疗法的改进取决于对抗肿瘤 T 细胞反应的更好理解。通过研究人类肿瘤引流淋巴结（TDLN），我们发现 TDLN 中激活的 CD8 T 细胞与肿瘤中的 TCF1 干细胞样细胞具有相同的功能、转录和表观遗传特征。表型和 TCR 重叠表明这些 TDLN 细胞是肿瘤驻留干细胞样 CD8 T 细胞的前体。小鼠肿瘤模型显示，肿瘤特异性 CD8 T 细胞在 TDLN 中被激活，但缺乏效应表型。这些干细胞样细胞迁移到肿瘤中，抗原呈递细胞的额外共刺激驱动效应细胞分化。这种响应癌症的 CD8 T 细胞激活模型不同于典型的 CD8 T 细胞激活急性病毒的模型，它提出了肿瘤特异性 CD8 T 细胞激活的两个阶段：TDLN 中的初始激活和随后的效应程序在 TDLN 中的获取。额外的共刺激后的肿瘤。
更新日期：2022-12-28
中文翻译：
癌症中 CD8+ T 细胞的激活包括淋巴结中的初始激活阶段，随后是肿瘤内的效应细胞分化
肿瘤免疫疗法的改进取决于对抗肿瘤 T 细胞反应的更好理解。通过研究人类肿瘤引流淋巴结（TDLN），我们发现 TDLN 中激活的 CD8 T 细胞与肿瘤中的 TCF1 干细胞样细胞具有相同的功能、转录和表观遗传特征。表型和 TCR 重叠表明这些 TDLN 细胞是肿瘤驻留干细胞样 CD8 T 细胞的前体。小鼠肿瘤模型显示，肿瘤特异性 CD8 T 细胞在 TDLN 中被激活，但缺乏效应表型。这些干细胞样细胞迁移到肿瘤中，抗原呈递细胞的额外共刺激驱动效应细胞分化。这种响应癌症的 CD8 T 细胞激活模型不同于典型的 CD8 T 细胞激活急性病毒的模型，它提出了肿瘤特异性 CD8 T 细胞激活的两个阶段：TDLN 中的初始激活和随后的效应程序在 TDLN 中的获取。额外的共刺激后的肿瘤。
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