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

A 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...

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Veröffentlicht in:Frontiers in immunology Jg. 14; S. 1334408
Hauptverfasser: Wang, Duo, Huang, Liuying, Qian, Danqi, Cao, Yulin, Wu, Xiaohan, Xu, Peiwen, Ming, Liang, Tang, Junhui, Huang, Zhaohui, Yin, Yuan, Zhou, Leyuan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media SA 08.01.2024
Frontiers Media S.A
Schlagworte:
Adenocarcinoma
Adenocarcinoma - radiotherapy
Adenocarcinoma of Lung - radiotherapy
Alcohol
Animals
Antibodies
Antigens
Antitumor activity
Cancer therapies
CD8 antigen
Dendritic cells
Disease Models, Animal
Humans
Immunology
Immunotherapy
low dose radiotherapy
Lung cancer
Lung Neoplasms - radiotherapy
Lymphocytes T
Maturation
Medical prognosis
Medical research
Mice
Optimization techniques
Patients
PD-1 protein
Prognosis
Proto-Oncogene Proteins p21(ras) - genetics
Radiation therapy
Risk factors
Tertiary Lymphoid Structures
tumor microenvironment
Tumors
lung cancer
low dose radiotherapy
tumor microenvironment
immunotherapy
tertiary lymphoid structures
ISSN:1664-3224, 1664-3224
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Zusammenfassung:A 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. Tissue 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. TLS+, TLS , TLS+GC+ and CD8 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. We 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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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Edited by: Tiezheng Hou, University College London, United Kingdom
Shisuo Du, Fudan University, China
Minghui Cao, University of California, San Diego, United States
Reviewed by: Lei Dong, Nanjing University, China
Xu Zhang, Jiangsu University, China
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1334408