Table3_Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma.xlsx

Lung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendous thrust to further improve the efficacy of immunotherapy in individual patients with LUAD. The suppression of T cells and their effector functions in the tumor microenvironment (TME) of LUAD is one of the primary reasons for the low efficacy of immunotherapy in some patients with LUAD. Therefore, identifying positive regulators of T cell proliferation (TPRs) may offer novel avenues for LUAD immunotherapy. In this study, we comprehensively evaluated the infiltration patterns of TPRs in 1,066 patients with LUAD using unsupervised consensus clustering and identified correlations with genomic and clinicopathological characteristics. Three infiltrating TPR clusters were defined, and a TPR-related risk signature composed of nine TPRs was constructed using least absolute shrinkage and selection operator-Cox regression algorithms to classify the individual TPR infiltration patterns. Cluster 1 exhibited high levels of T cell infiltration and activation of immune-related signaling pathways, whereas cluster 2 was characterized by robust T cell immune infiltration and enrichment of pathways associated with carcinogenic gene sets and tumor immunity. Cluster 3 was characterized as an immune-desert phenotype. Moreover, the TPR signature was confirmed as an independent prognostic biomarker for drug sensitivity in patients with LUAD. In conclusion, the TPR signature may serve as a novel tool for effectively characterizing immune characteristics and evaluating the prognosis of patients with LUAD.

肺腺癌（Lung adenocarcinoma, LUAD）是全球范围内最常见且致死率最高的恶性肿瘤类型之一。近年来，免疫治疗已广泛应用于肺腺癌患者的临床治疗，并被证实可有效改善患者预后，但目前仍亟需进一步提升该疗法在个体肺腺癌患者中的治疗效果。肺腺癌肿瘤微环境（Tumor microenvironment, TME）中T细胞的功能抑制及其效应功能受损，是部分肺腺癌患者免疫治疗疗效不佳的核心原因之一。因此，筛选T细胞增殖正调控因子（positive regulators of T cell proliferation, TPRs）有望为肺腺癌免疫治疗提供全新的干预策略。本研究通过无监督共识聚类方法，全面分析了1066例肺腺癌患者体内TPRs的浸润模式，并明确了其与基因组特征及临床病理特征的相关性。研究共确定了三种TPRs浸润亚型，并借助最小绝对收缩和选择算子-Cox回归算法，构建了由9种TPRs组成的TPRs相关风险评分模型，以实现对个体TPRs浸润模式的分类。其中，亚型1表现为高水平T细胞浸润及免疫相关信号通路激活；亚型2以显著的T细胞免疫浸润为特征，并富集致癌基因集与肿瘤免疫相关通路；亚型3则呈现免疫沙漠表型。此外，本研究证实TPRs相关风险模型可作为独立的预后生物标志物，用于预测肺腺癌患者的药物敏感性。综上，TPRs相关风险模型可作为一种全新的工具，有效表征肺腺癌患者的免疫特征并评估其预后。