Department of Medical, Oral, and Biotechnology Science, University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy.
Center for Advanced Studies and Technology (CAST), University "G. d'Annunzio" Chieti-Pescara, 66100 Chieti, Italy.
Int J Mol Sci. 2022 Jun 9;23(12):6473. doi: 10.3390/ijms23126473.
In human medicine, the progression from early neoplasia development to either complete resolution of tumorigenesis and associated inflammation or chronicity and fatal outcomes remain difficult to predict. Resolution of inflammation is an active process that stimulates the termination of the inflammatory response and promotes return to homeostasis, while failure in resolution contributes to the development of a number of diseases. To understand how resolution pathways contribute to tumorigenesis, we defined and employed a cumulative score based on the expression level of genes involved in synthesis, signaling, and metabolism of the D-series resolvin (RvD). This score was used for comparative analyses of clinical, cellular, and molecular features of tumors, based on RNA-sequencing (RNA-seq) datasets collected within The Cancer Genome Atlas (TCGA) program. Our results indicate that higher RvD scores are associated with better clinical outcome of patients with head and neck squamous cell carcinoma (HNSC), and with molecular and cellular signatures indicative of enhanced anti-tumor immunity and better response to immune-checkpoint inhibitors (ICI), also in human papilloma virus (HPV) negative HNSC subtypes. Thus, higher activity of the RvD pathway identifies patients with improved resolution and a more efficient immune reaction against cancer.
在人类医学中，从早期肿瘤发生发展到肿瘤发生和相关炎症的完全消退或慢性化和致命结局的进展仍然难以预测。炎症的消退是一个活跃的过程，它刺激炎症反应的终止，并促进恢复到体内平衡，而消退的失败则导致许多疾病的发生。为了了解消退途径如何促进肿瘤发生，我们定义并采用了基于参与 D 系列分辨率素（RvD）合成、信号转导和代谢的基因表达水平的累积评分。该评分用于基于癌症基因组图谱（TCGA）计划中收集的 RNA 测序（RNA-seq）数据集对肿瘤的临床、细胞和分子特征进行比较分析。我们的结果表明，较高的 RvD 评分与头颈部鳞状细胞癌（HNSC）患者更好的临床结局相关，并且与分子和细胞特征一致，表明增强了抗肿瘤免疫和对免疫检查点抑制剂（ICI）的更好反应，在 HPV 阴性 HNSC 亚型中也是如此。因此，RvD 途径的更高活性可识别出具有改善消退和对癌症更有效的免疫反应的患者。
