作为免疫治疗的主要执行者，T细胞显著影响了免疫治疗的疗效。然而，T细胞增殖调节因子对肺腺癌（LUAD）预后和免疫治疗的贡献仍不清楚。基于T细胞增殖调节因子，从癌症基因组图谱（TCGA）中将LUAD样本分为两个不同的聚类，构建了与预后相关的T细胞增殖调节因子（TPR）签名，结合临床信息建立了一个实用的标准图。该签名的预测能力通过额外的基因表达整合库（GEO）数据集得到验证。我们还分析了不同亚组的肿瘤微环境（TME）差异，并根据TIDE算法预测免疫治疗的响应。最后，我们通过ADA（腺苷脱氨酶）敲减进一步探索了ADA在肺腺癌细胞系中的作用。根据共识聚类，两个不同的分子亚型在存活和肿瘤微环境方面存在差异。T细胞增殖调节因子相关的标记可以准确预测LUAD的预后。低风险组的免疫浸润水平较高，免疫相关通路更丰富，并且与高风险组相比，对免疫治疗的反应显著更好（χ2检验，p < 0.0001）。 ADA的敲减抑制了肺腺癌细胞株的增殖、迁移和侵袭。T细胞增殖调节因子与LUAD患者的预后和肿瘤微环境密切相关。该标记可以很好地预测LUAD患者的预后和对免疫治疗的反应。 ADA可能成为LUAD治疗的新靶点。 版权所有©2023 Chang、Li、Cheng、He、Ou及Wang。

As the main executor of immunotherapy, T cells significantly affect the efficacy of immunotherapy. However, the contribution of the T cell proliferation regulator to the prognosis of lung adenocarcinoma (LUAD) and immunotherapy is still unclear.Based on T cell proliferation regulators, LUAD samples from The Cancer Genome Atlas (TCGA) were divided into two different clusters by consensus clustering. Subsequently, the T cell proliferation regulator (TPR) signature was constructed according to the prognostic T cell proliferation regulators. Combined with clinical information, a nomogram for clinical practice was constructed. The predictive ability of the signature was verified by the additional Gene Expression Omnibus (GEO) dataset. We also analyzed the differences of tumor microenvironment (TME) in different subgroups and predicted the response to immunotherapy according to the TIDE algorithm. Finally, we further explored the role of ADA (Adenosine deaminase) in the lung adenocarcinoma cell lines through the knockdown of ADA.According to the consensus clustering, there were differences in survival and tumor microenvironment between two different molecular subtypes. T cell proliferation regulator-related signature could accurately predict the prognosis of LUAD. The low-risk group had a higher level of immune infiltration and more abundant immune-related pathways, and its response to immunotherapy was significantly better than the high-risk group (Chi-square test, p<0.0001). The knockdown of ADA inhibited proliferation, migration, and invasion in lung adenocarcinoma cell lines.T cell proliferation regulators were closely related to the prognosis and tumor microenvironment of LUAD patients. And the signature could well predict the prognosis of LUAD patients and their response to immunotherapy. ADA may become a new target for the treatment of LUAD.Copyright © 2023 Chang, Li, Cheng, He, Ou and Wang.