Distinct prognostic value of circulating anti-telomerase CD4+ Th1 immunity and exhausted PD-1+/TIM-3+ T cells in lung
Distinct prognostic value of circulating anti-telomerase CD4+ Th1 immunity and exhausted PD-1+/TIM-3+ T cells in lung
复制标题
DOI：
10.1038/s41416-019-0531-5
复制
发表时间：
2019-08-27
影响因子：
8.8
通讯作者：
Adotevi, Olivier
中科院分区：
文献类型：
--
作者：
Laheurte, Caroline;Dosset, Magalie;Adotevi, Olivier
背景技术背景：尽管Th 1极化的CD 4（+）T细胞在癌症免疫监视中起着关键作用，但将其潜力转化为临床应用仍然具有挑战性。方法：采用酶联免疫斑点法（ELISpot）检测170例非小细胞肺癌（NSCLC）患者外周血中的抗肿瘤Th 1细胞免疫应答，并分析其临床意义。流式细胞仪进行血液免疫细胞表型分析。结果：在任何治疗前，35%的NSCLC患者检测到TERT反应性CD 4 T细胞反应。功能分析表明，这些细胞是效应记忆和Th 1极化，能够产生效应细胞因子，如IFN-γ，TNF-α和IL-2。抗-TERT Th 1应答的存在与耗尽的PD-1（+）/TIM-3（+）CD 4 T细胞的水平呈负相关。这两个免疫参数的水平对生存期的影响不同，因此抗-TERTTh 1应答水平的升高和PD-1（+）TIM-3（+）CD 4（+）T细胞耗竭率的降低与较好的预后相关。这项研究强调了监测循环抗肿瘤Th 1应答对患者分层和治疗决策的潜在意义。
BACKGROUND: Despite the critical roles of Th1-polarised CD4(+) T cells in cancer immunosurveillance, the translation of their potential to clinical use remains challenging. Here, we investigate the clinical relevance of circulating antitumor Th1 immunity in non-small cell lung cancer (NSCLC).METHODS: The circulating antitumor Th1 response was assessed by the ELISpot assay in 170 NSCLC patients using a mixture of HLA class II-restricted peptides from telomerase (TERT). Phenotyping of blood immune cells was performed by flow cytometry.RESULTS: TERT-reactive CD4 T-cell response was detected in 35% of NSCLC patients before any treatment. Functional analysis showed that these cells were effector memory and Th1 polarised capable to produce effector cytokines, such as IFN-gamma, TNF-alpha and IL-2. The presence of anti-TERT Th1 response was inversely correlated with the level of exhausted PD-1(+)/TIM-3(+)CD4 T cells. The level of these two immune parameters differentially affected the survival, so that increased level of anti-TERT Th1 response and low rate of exhausted PD-1(+)TIM-3(+)CD4(+) T cells were associated with a better prognosis.CONCLUSIONS: Systemic anti-TERT Th1 response plays a strong antitumor protective role in NSCLC. This study underlines the potential interest of monitoring circulating antitumor Th1 response for patients' stratification and therapy decision.