The adenosine-signaling axis has been recognized as an important immunomodulatory pathway in tumor immunity. However, the biological role of the adenosine-signaling axis in the remodeling of the tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unclear. Here, we quantified adenosine signaling (ado_sig) in LUAD samples using the GSVA method and assessed the prognostic value of adenosine in LUAD. Afterward, we explored the heterogeneity of the tumor-immune microenvironment at different adenosine levels. In addition, we analyzed the potential biological pathways engaged by adenosine. Next, we established single-cell transcriptional profiles of LUAD and analyzed cellular composition and cell-cell communication analysis under different adenosine microenvironments. Moreover, we established adenosine-related prognostic signatures (ARS) based on comprehensive bioinformatics analysis and evaluated the efficacy of ARS in predicting immunotherapy. The results demonstrated that adenosine signaling adversely impacted the survival of immune-enriched LUAD. The high-adenosine microenvironment exhibited elevated pro-tumor-immune infiltration, including M2 macrophages and displayed notably increased epithelial-mesenchymal transition (EMT) transformation. Furthermore, adenosine signaling displayed significant associations with the expression patterns and prognostic value of immunomodulators within the TME. Single-cell sequencing data revealed increased fibroblast occupancy and a prominent activation of the SPP1 signaling pathway in the high adenosine-signaling microenvironment. The ARS exhibited promising effectiveness in prognostication and predicting immunotherapy response in LUAD. In summary, overexpression of adenosine can cause a worsened prognosis in the LUAD with abundant immune infiltration. Moreover, increased adenosine levels are associated with pro-tumor-immune infiltration, active EMT transformation, pro-tumor angiogenesis, and other factors promoting cancer progression, which collectively contribute to the formation of an immunosuppressive microenvironment. Importantly, the ARS developed in this study demonstrate high efficacy in evaluating the response to immunotherapy.

腺苷信号轴已被认为是肿瘤免疫中重要的免疫调节途径。然而，腺苷信号轴在肺腺癌（LUAD）肿瘤微环境（TME）重塑中的生物学作用仍不清楚。在这里，我们使用 GSVA 方法量化 LUAD 样本中的腺苷信号传导 (ado_sig)，并评估腺苷在 LUAD 中的预后价值。随后，我们探讨了不同腺苷水平下肿瘤免疫微环境的异质性。此外，我们分析了腺苷参与的潜在生物学途径。接下来，我们建立了 LUAD 的单细胞转录谱，并分析了不同腺苷微环境下的细胞组成和细胞间通讯分析。此外，我们基于综合生物信息学分析建立了腺苷相关预后特征（ARS），并评估了 ARS 在预测免疫治疗方面的功效。结果表明，腺苷信号传导对免疫富集的 LUAD 的存活产生不利影响。高腺苷微环境表现出促肿瘤免疫浸润升高，包括 M2 巨噬细胞，并显着增加上皮间质转化 (EMT) 转化。此外，腺苷信号传导与 TME 内免疫调节剂的表达模式和预后价值显着相关。单细胞测序数据显示，在高腺苷信号微环境中，成纤维细胞占有率增加，SPP1 信号通路显着激活。ARS 在预测和预测 LUAD 免疫治疗反应方面表现出有希望的有效性。总之，腺苷的过度表达会导致免疫浸润丰富的 LUAD 预后恶化。此外，腺苷水平升高与促肿瘤免疫浸润、活跃的EMT转化、促肿瘤血管生成和其他促进癌症进展的因素有关，这些因素共同促进了免疫抑制微环境的形成。重要的是，本研究中开发的 ARS 在评估免疫治疗反应方面表现出高效能。