The role and prognostic impact of Flt3L/OX40L co-expression characteristics in remodeling the immune microenvironment of non-small cell lung cancer

CHEN Chen; CHEN Chao; ZHU Junmeng; HUANG Xing; LIU Baorui

doi:10.3969/j.issn.1009-0460.2025.05.006

Abstract：Objective To investigate the expression characteristics of Flt3L and OX40L in non-small cell lung cancer(NSCLC),and their relationship with the tumor immune microenvironment and clinical prognosis,evaluating their potential as immune therapy targets.Methods Tissue microarray(TMA)and multiplex immunofluorescence(mIF)techniques were used to analyze the expression of Flt3L and OX40L in tumor and stromal regions from 115 NSCLC patients.Kaplan-Meier survival analysis and Cox regression models were employed to assess the correlation between the expression of Flt3L and OX40L and patient prognosis,and to examine their relationship with immune cell infiltration and immune checkpoint molecules.Results The expression of Flt3L and OX40L in the stromal region was significantly higher than in the tumor region(Flt3L_stroma vs.Flt3L_tumor:73.9%vs.33.9%;OX40L_stroma vs.OX40L_tumor:72.2%vs.70.4%).The co-expression of Flt3L and OX40L in the stroma was observed in 62.6%of patients.Kaplan-Meier survival analysis revealed that high expression of OX40L in the tumor stroma was significantly associated with better survival(P=0.001),and co-expression of Flt3L and OX40L in the stroma was also linked to improved survival(P=0.017).Cox regression analysis further confirmed that high expression of Flt3L and OX40L in the tumor stroma was associated with reduced mortality risk(HR=0.493,P=0.008;HR=0.495,P=0.005),and co-expression of Flt3L and OX40L significantly improved patient survival(HR=0.548,P=0.019).Additionally,high expression of Flt3L was associated with increased infiltration of CD8+T cells and M1 macrophages,while high expression of OX40L was associated with an increase in both CD4+and CD8+T cells.However,neither molecule significantly influenced the infiltration of Tregs or M2 macrophages.Conclusion The expression of Flt3L and OX40L in the NSCLC immune microenvironment is closely related to patient prognosis.Their high expression likely enhances anti-tumor immune responses by promoting T cell infiltration and macrophage activation,improving survival outcomes.The co-expression of Flt3L and OX40L shows promise as a potential immune therapy target.Future studies should further explore their clinical application potential,particularly in combination therapies for immune treatment.