Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun 130021, China.
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun 130021, China.
Mol Immunol. 2022 Jul;147:40-49. doi: 10.1016/j.molimm.2022.04.005. Epub 2022 Apr 30.
The tumour microenvironment reshapes the specific gene expression of regulatory T cells (Tregs). A better definition of Treg subpopulations in the non-small-cell lung cancer (NSCLC) milieu is expected to clarify the identity and functional mode of Tregs and lead to the identification of better therapeutic targets.
A total of 53 peripheral blood (PB) samples from 36 NSCLC patients and 17 control subjects and 42 matched bronchoalveolar lavage fluid (BALF) samples from 31 NSCLC patients and 11 control subjects were obtained to examine the frequencies of Treg subgroups through flow cytometry. Fifteen PB samples from healthy individuals were collected to explore the differential functions of Treg subsets. The PB samples of 5 patients after chemotherapy were obtained to evaluate the effect of chemotherapy on Treg subsets. Serum CYFRA 21-1 levels in NSCLC patients were determined using an electrochemiluminescence immunoassay.
The proportions of CD4CD25FoxP3 Tregs in both PB and BALF were increased in NSCLC patients compared to controls. In BALF, the TIGIT, Helios, and TIGITHelios Treg subset levels were significantly elevated; the levels of the last two subsets were associated with NSCLC development, while the level of TIGITHelios Tregs was decreased. The proportions of overall Tregs and TIGIT, Helios, and HeliosTIGIT Tregs were positively correlated with the serum CYFRA 21-1 levels in all patients. Functional differences were observed between HeliosTIGIT and HeliosTIGIT Tregs. After chemotherapy, regardless of the reduction in serum CYFRA 21-1 levels, the proportions of Tregs and Treg subsets did not change.
Elevated TIGITHelios and Helios Treg levels may play a role in NSCLC tumour progression, and targeting TIGIT and Helios on Tregs may be an effective treatment for NSCLC.
肿瘤微环境重塑调节性 T 细胞（Tregs）的特定基因表达。更好地定义非小细胞肺癌（NSCLC）环境中的 Treg 亚群有望阐明 Tregs 的身份和功能模式，并有助于确定更好的治疗靶点。
共获取 36 名 NSCLC 患者和 17 名对照者的 53 份外周血（PB）样本，以及 31 名 NSCLC 患者和 11 名对照者的 42 份配对支气管肺泡灌洗液（BALF）样本，通过流式细胞术检查 Treg 亚群的频率。采集 15 份健康个体的 PB 样本以探索 Treg 亚群的差异功能。获取 5 名化疗后患者的 PB 样本以评估化疗对 Treg 亚群的影响。使用电化学发光免疫分析法测定 NSCLC 患者血清中 CYFRA 21-1 水平。
与对照组相比，NSCLC 患者 PB 和 BALF 中 CD4CD25FoxP3 Tregs 的比例均升高。在 BALF 中，TIGIT、Helios 和 TIGITHelios Treg 亚群水平显著升高；后两个亚群的水平与 NSCLC 的发生相关，而 TIGITHelios Tregs 的水平降低。所有患者中，总 Tregs 以及 TIGIT、Helios 和 HeliosTIGIT Tregs 的比例与血清 CYFRA 21-1 水平呈正相关。HeliosTIGIT 和 HeliosTIGIT Tregs 之间观察到功能差异。化疗后，无论血清 CYFRA 21-1 水平降低与否，Tregs 和 Treg 亚群的比例均未改变。
TIGITHelios 和 Helios Treg 水平的升高可能在 NSCLC 肿瘤进展中发挥作用，针对 Tregs 上的 TIGIT 和 Helios 可能是治疗 NSCLC 的有效方法。
