[Clinical Significance and Future Prospects of Tertiary Lymphoid Structure in Lung Cancer].

Abstract

Lung cancer remains one of the leading causes of cancer‒related mortality worldwide, underscoring the urgent need for innovative diagnostic and therapeutic approaches. The advent of immune checkpoint inhibitors(ICIs)has significantly transformed the treatment landscape, particularly for non‒small cell lung cancer(NSCLC). However, predictive biomarkers for ICI efficacy remain limited, with PD‒L1 expression, tumor mutational burden(TMB), and microsatellite instability providing only partial insight into therapeutic response. Recent attention has focused on tertiary lymphoid structures(TLS), ectopic lymphoid aggregates resembling secondary lymphoid organs that form in the tumor microenvironment. TLS are composed of B cells, T cells, dendritic cells, and other immune components, and play a central role in coordinating local antitumor immune responses. In NSCLC, the presence of TLS has been associated with favorable prognosis and improved response to ICIs, independent of PD‒L1 or TMB status. Moreover, emerging evidence suggests that the quality of TLS-such as the degree of maturation and the nature of infiltrating immune cells-may further influence immunotherapeutic outcomes. This review outlines the clinical significance of TLS in lung cancer, discussing their structure, function, and potential as novel biomarkers for stratifying patients undergoing immunotherapy. We also explore future directions including therapeutic strategies aimed at promoting TLS formation, such as vaccines or immune adjuvants, as well as the application of artificial intelligence and spatial omics technologies for the standardized evaluation and in‒depth characterization of TLS. As the integration of TLS analysis into clinical oncology evolves, a more precise and personalized approach to lung cancer immunotherapy may be realized.