Wouldn't you like to know: are tertiary lymphoid structures necessary for lung defence?

Curtis, Jeffrey L.

doi:10.1183/13993003.04352-2020

Cited by 2 publications

(1 citation statement)

References 64 publications

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“…TLSs are characterized by their vascularization and consist of T-cell regions containing mature dendritic cells, germinal centers with follicular dendritic cells and proliferating B cells, and high endothelial venules (HEV/PNAd) ( 8 ). TLSs have been linked to a positive prognosis in various types of cancer, including lung cancer ( 9 ), colorectal cancer ( 10 ), melanoma ( 11 ), and pancreatic cancer ( 12 ). Recently, numerous reports have shown that TLSs can enhance the response to immune checkpoint inhibitors (ICIs) treatment ( 13 , 14 ).…”

Section: Introductionmentioning

confidence: 99%

Low-dose radiotherapy promotes the formation of tertiary lymphoid structures in lung adenocarcinoma

Wang,

Huang,

Qian

et al. 2024

Front. Immunol.

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PurposeA tertiary lymphoid structure (TLS) refers to an organized infiltration of immune cells that is linked to a positive prognosis and improved response to immunotherapy. However, methods that promote TLS formation are limited and challenging to implement in clinical settings. In this study, we aimed to promote the formation and maturation of TLSs in lung adenocarcinoma (LUAD) by combining low-dose radiotherapy (LDRT) with immunotherapy.MethodsTissue sections from 198 patients who had undergone surgery were examined. Risk factors for patient survival were assessed, and the relationship between TLSs and five-year survival was analyzed. The Kras-LSL-G12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. LDRT combined with anti-PD-1 was used to promote the formation and maturation of TLSs.ResultsTLS+, TLSHigh, TLS+GC+ and CD8High within TLS+ were associated with a favorable prognosis. LDRT increased the formation of early TLSs in the Kras-LSL-G12D lung cancer mouse model. In addition, LDRT combined with anti-PD-1 treatment can significantly improve the maturity of TLSs in mouse LUAD, resulting in greater antitumor effects. This antitumor effect was strongly associated with the number of CD8+ T cells within the TLSs.ConclusionWe successfully applied LDRT combined with PD-1 inhibitor therapy for the first time, which increased both the quantity and maturity of TLSs in lung cancer. This approach achieved a promising antitumor effect.

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