Single-cell omics in tumor lymph node metastasis: mechanisms and therapeutic implications

Lymph node metastasis (LNM) represents a distinctive stage in cancer progression, exerting a profound impact on patient prognosis. Accumulating studies have unveiled that tumor-draining lymph nodes (TDLNs) play a pivotal role in immunotherapy, functioning as an armory for anti-tumor immunity. Concurrently, LNM itself accelerates systemic metastatic progression, exacerbates systemic immunosuppression, and in turn fuels tumor progression. Recent advancements in single-cell sequencing technology have furnished insights into the mechanisms of LNM at single-cell resolution, unraveling the process of LNM in tumor cells and accompanying microenvironmental alterations from the perspectives of cellular heterogeneity, intercellular communication, and cellular evolutionary trajectories. Furthermore, single-cell sequencing studies have underscored the critical role of TDLNs in immunotherapy and their corresponding adaptive modifications. This article reviews the LNM microenvironment and immunosuppressive mechanisms revealed by single-cell sequencing technology, summarizes the novel targets for LNM and the current status of LNM-related immunotherapy research, and outlines the current challenges and future development directions from both technological and research content perspectives.