The multi-omics landscape of lung adenocarcinoma evolution: deciphering metabolic reprogramming-driven immune escape and its implications in combined therapy.
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引用次数: 0
Abstract
The progression of lung adenocarcinoma (LUAD) from pre-invasive lesions (atypical adenomatous hyperplasia/adenocarcinoma in situ) to invasive adenocarcinoma constitutes a complex, multi-dimensional, and dynamic process. While the genomic drivers underlying this transition have been extensively characterized, the mechanisms by which metabolic reprogramming remodels the tumor immune microenvironment to orchestrate immune escape remain a critical knowledge gap. Leveraging insights from multi-omics integration encompassing genomics, metabolomics, single-cell RNA sequencing, and spatial transcriptomics, this review systematically delineates the molecular mechanisms through which metabolic reprogramming acts as a pivotal driver of immune escape during LUAD evolution. We critically dissect the intricate metabolic-epigenetic-spatial-immune; specifically, we highlight the mechanism through which cancer cells impair immune effector function via nutrient deprivation and utilize oncometabolites to instigate epigenetic modifications, thereby imprinting an immunosuppressive phenotype at the genetic level. Furthermore, this review discusses the development of early-screening biomarkers based on metabolic signatures, as well as combination therapeutic strategies targeting dual metabolic-immune checkpoints. The aim is to provide a novel theoretical framework for improving clinical management and prognosis in patients with LUAD.
期刊介绍：
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.
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