Effect of tumor draining lymph nodes in the formation and maturation of tertiary lymphoid structure in patients with lung adenocarcinoma.

BACKGROUND: Tertiary lymphoid structures (TLSs), ectopic lymphoid aggregates composed of immune cells, are associated with favorable clinical outcomes and increased efficacy of anti-tumor immunotherapies. However, the mechanisms underlying the formation and maturation of TLSs require further elucidation. The correlation between tumor immune microenvironment in tumor-draining lymph nodes (TDLNs) and TLSs remains inadequately studied. The study aimed to utilize multiplex immunofluorescence (mIF) to explore the relationship between TDLN and TLSs. METHODS: Tissue slides from 120 patients with lung adenocarcinoma (LUAD) were collected to perform for mIF staining. Panel 1 (DAPI, CD20, CD21, CD23) was used for the quantitative and qualitative analyses of TLS. Panel 2 (DAPI, CD4, CD8, CD20) was used to describe the immune microenvironment of the tumor and TDLN. RESULTS: TLS (+) patients showed better disease-free survival (DFS) (mDFS, 70.8 vs. 28.7 months; p = 0.013, HR = 0.555, 95% CI 0.352 to 0.875) and overall survival (OS) (mOS, 77.83 months vs. not reached; p = 0.028, HR = 0.512, 95% CI 0.289 to 0.907) compared to TLS (-) patients. B cells in the tumor and TDLN determined the formation of TLSs. A higher percentage of B cells in the tumor / B cells in the TDLN correlated with a higher number of TLSs (p < 0.0001, r = 0.349). In addition, a high percentage of TIM-1 + B cells /B cells in the TDLN was correlated with a reduced percentage of mature TLSs (p < 0.001, r=-0.441). CONCLUSION: This study demonstrated that B cells in the tumor and TDLN play critical roles in the formation and maturation of TLS. TIM-1 + B cell is a unique immunosuppressive B cell subset that impedes the maturation of TLS and could be a promising target for improving the maturation of TLS and the prognosis of LUAD.