CD4(+) T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer.
CD4(+) T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer.
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需要 CD4 T 细胞来提高 CIK 治疗非小细胞肺癌的疗效
DOI：
10.1038/s41419-022-04882-x
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发表时间：
2022-05-06
影响因子：
9
通讯作者：
Ren, Xiubao
中科院分区：
文献类型：
--
作者：
Liu, Shaochuan;Meng, Yuan;Liu, Liang;Lv, Yingge;Yu, Wenwen;Liu, Ting;Wang, Limei;Mu, Di;Zhou, Qiuru;Liu, Min;Ren, Yulin;Zhang, Dong;Li, Baihui;Sun, Qian;Ren, Xiubao
作为一种广泛研究的过继治疗方法，CIK（细胞因子诱导的杀伤细胞）治疗在许多针对非小细胞肺癌的临床试验中显示出临床益处。然而，CIK细胞作为异质细胞群，其疗效具有很强的不稳定性和个体差异，受到肿瘤微环境和CIK亚群的协同调节。其中，CD4+ T细胞属于CIK细胞群的重要亚群，其对CIK治疗的影响尚不清楚。在此，我们展示了 CD4+ T 细胞如何正向调节 CD3+ CD56+ T 和 CD3+ CD8+ T 细胞的功能。在此过程中，我们发现Th1/Th17 CD4+亚群可以通过分泌IL-17A诱导AKT通路磷酸化，并上调T-bet/Eomes转录因子的表达，从而恢复CD8+/CD3+CD56+ T细胞的功能，逆转PD-1+Tim-3+ T细胞的耗竭。这些研究结果将为临床筛选CIK治疗合适人群以及制定CIK治疗加免疫检查点治疗策略提供指导。基于这些发现，我们正在进行一项开放标签的II期研究（NCT04836728），旨在评估自体CIK联合PD-1抑制剂一线治疗IV型NSCLC的效果，并希望在该临床试验中观察患者的获益。在此，Liu 及其同事表明，细胞因子诱导杀伤 (CIK) 细胞中的 CD4+ T 细胞是增强 CIK 治疗临床疗效所必需的。此外，CD4+ T 细胞通过产生 IL-17A 来帮助恢复 CD8+/CD3+CD56+ T 细胞的功能并逆转 CIK 治疗中 PD-1+TIM-3+ T 细胞的耗竭至关重要。
As a widely studied adoptive treatment method, CIK (cytokine-induced killer cells) treatment has shown clinical benefits in many clinical trials on non-small cell lung cancer. As a heterogeneous cell population, however, CIK cells have a strong instability and individual differences in their efficacies, which are collaboratively regulated by the tumor microenvironment and CIK subpopulations. Among them, CD4+ T cells belong to a crucial subgroup of the CIK cell population, and their influence on CIK therapy is still unclear. Herein, we show how CD4+ T cells positively regulate the functions of CD3+CD56+ T and CD3+CD8+ T cells. During this process, we found that Th1/Th17 CD4+ subgroups can induce the phosphorylation of the AKT pathway by secreting IL-17A, and upregulate the expression of T-bet/Eomes transcription factors, thereby restoring the function of CD8+/CD3+CD56+ T cells and reversing the exhaustion of PD-1+Tim-3+ T cells. These findings will provide guidance for the clinical screening of suitable populations for CIK treatment and formulation of strategies for CIK therapy plus immune checkpoint treatment. Based on these findings, we are conducting an open-label phase II study (NCT04836728) is to evaluate the effects of autologous CIKs in combination with PD-1 inhibitor in the first-line treatment of IV NSCLC, and hope to observe patients’ benefits in this clinical trial. Herein, Liu and colleagues show that CD4+ T cells in cytokine-induced killer (CIK) cells are required to enhance the clinical efficacy of CIK therapy. In addition, CD4+ T cells help via IL-17A production is critical to restoring the function of CD8+/CD3+CD56+ T cells and reversing the exhaustion of PD-1+TIM-3+ T cells in CIK therapy.
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影响因子：
7.5
作者：
Franco, Marina Santiago;Roque, Marjorie Coimbra;Oliveira, Monica Cristina
通讯作者：
Oliveira, Monica Cristina
DOI：
10.1038/nri2888
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29.4
作者：
Lee, Joon Hyeok;Lee, Jeong-Hoon;Yoon, Jung-Hwan
通讯作者：
Yoon, Jung-Hwan
DOI：
10.1084/jem.20112495
发表时间：
2013-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iborra S;Ramos M;Arana DM;Lázaro S;Aguilar F;Santos E;López D;Fernández-Malavé E;Del Val M
通讯作者：
Del Val M
影响因子：
13
作者：
Cappuzzello, Elisa;Sommaggio, Roberta;Rosato, Antonio
通讯作者：
Rosato, Antonio