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.