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Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells.
Immunity ( IF 25.5 ) Pub Date : 2019-01-08 , DOI: 10.1016/j.immuni.2018.11.014 Sema Kurtulus 1 , Asaf Madi 2 , Giulia Escobar 1 , Max Klapholz 1 , Jackson Nyman 3 , Elena Christian 3 , Mathias Pawlak 1 , Danielle Dionne 3 , Junrong Xia 1 , Orit Rozenblatt-Rosen 3 , Vijay K Kuchroo 1 , Aviv Regev 4 , Ana C Anderson 1
Immunity ( IF 25.5 ) Pub Date : 2019-01-08 , DOI: 10.1016/j.immuni.2018.11.014 Sema Kurtulus 1 , Asaf Madi 2 , Giulia Escobar 1 , Max Klapholz 1 , Jackson Nyman 3 , Elena Christian 3 , Mathias Pawlak 1 , Danielle Dionne 3 , Junrong Xia 1 , Orit Rozenblatt-Rosen 3 , Vijay K Kuchroo 1 , Aviv Regev 4 , Ana C Anderson 1
Affiliation
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An improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1- TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8+ T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7/Tcf1 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8+ T cell responses upon immunotherapy.
中文翻译：
检查点封锁免疫疗法可诱导PD-1-CD8 +肿瘤浸润T细胞动态变化。
对检查点封锁后的抗肿瘤CD8 + T细胞反应的更深入了解将使人们能够获得更明智和有效的治疗策略。在这里，我们检查了检查点封锁疗法后CD8 +肿瘤浸润淋巴细胞（TIL）的效应反应的动力学。在临床前模型中，Tim-3 + PD-1联合阻断后，CD8 + TIL的大体积和单细胞RNA谱显示PD-1- TIL的转录谱发生了显着变化。这些细胞可以分为具有幼稚，效应子和记忆前体样细胞特征的子集。效应子和记忆前体样TIL包含肿瘤抗原特异性细胞，表现出增殖和效应能力，并且在不同肿瘤模型中对不同检查点封锁疗法的反应有所扩展。记忆前体样亚群与患者对检查点封锁反应相关的CD8 + T细胞具有共同特征，并且在缺乏Tcf7的情况下受到损害。Tcf7 / Tcf1的表达是多种免疫疗法功效的必要条件，突显了这种转录调节因子在免疫疗法中发展有效CD8 + T细胞应答中的重要性。
更新日期：2019-01-08
中文翻译：
检查点封锁免疫疗法可诱导PD-1-CD8 +肿瘤浸润T细胞动态变化。
对检查点封锁后的抗肿瘤CD8 + T细胞反应的更深入了解将使人们能够获得更明智和有效的治疗策略。在这里，我们检查了检查点封锁疗法后CD8 +肿瘤浸润淋巴细胞（TIL）的效应反应的动力学。在临床前模型中，Tim-3 + PD-1联合阻断后，CD8 + TIL的大体积和单细胞RNA谱显示PD-1- TIL的转录谱发生了显着变化。这些细胞可以分为具有幼稚，效应子和记忆前体样细胞特征的子集。效应子和记忆前体样TIL包含肿瘤抗原特异性细胞，表现出增殖和效应能力，并且在不同肿瘤模型中对不同检查点封锁疗法的反应有所扩展。记忆前体样亚群与患者对检查点封锁反应相关的CD8 + T细胞具有共同特征，并且在缺乏Tcf7的情况下受到损害。Tcf7 / Tcf1的表达是多种免疫疗法功效的必要条件，突显了这种转录调节因子在免疫疗法中发展有效CD8 + T细胞应答中的重要性。
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