2679 - Targeting CCR6 to Modulate Low-Dose Radiotherapy and Tertiary Lymphoid Structure Formation in Non-Small Cell Lung Cancer
Presenter(s)
Y. Fang1, H. Pei2, and L. Zhou3; 1Soochow University, Suzhou, China, 2Soochow university, Suzhou, China, 3Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China
Purpose/Objective(s): Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates formed by the recruitment of immune cells, consistently associated with favorable clinical outcomes and enhanced anti-tumor immunity in malignant tumors. Low-dose radiotherapy (LDRT) has been demonstrated to promote the formation of TLS and augment immune cell infiltration. However, the underlying mechanisms remain largely elusive. Herein, this study aims to elucidate how LDRT modulates TLS and to investigate whether targeted modulation of the key gene C-C chemokine receptor 6 (CCR6) combined with LDRT can potentiate the formation and maturation of TLS in non-small cell lung cancer (NSCLC).
Materials/Methods: The CCSP-rtTA/TetO-Cre/LSL-KrasG12D spontaneous lung cancer mouse model was used to screen the optimal irradiation dose (0/1/2 Gy whole lung irradiation) for promoting TLS formation. Bulk RNA sequencing identified CCR6 as a key gene, and the combined effects of LDRT with CCR6 agonist or inhibitor on TLS formation and immune cell infiltration were further evaluated in this model.
Results: LDRT enhanced TLS formation in the mouse model, and LDRT treated mice exhibited prolonged overall survival. Combined treatment with LDRT and a CCR6 agonist further increased TLS numbers, suppressed tumor proliferation, and promoted the infiltration of immune cells, particularly CD8+ T cells, thereby exerting a more potent anti-tumor effect.
Conclusion: Our findings identify a critical role for CCR6 in LDRT induced TLS formation. The combination of LDRT and a CCR6 agonist effectively potentiates the anti-tumor response of TLS, supporting this regimen as a promising radioimmunotherapy strategy for NSCLC.