The role of spatial interplay patterns between PD-L1-positive tumor cell and T cell in recurrence of locally advanced non-small cell lung cancer

Abstract

Purpose: To explore the relationship between the spatial interaction of programmed death-ligand 1(PD-L1)-positive tumor cell and T cell with specific functions and the recurrence of non-small cell lung cancer (NSCLC) and optimize prognostic stratification.

Materials and methods: This study retrospectively included 104 patients with locally advanced NSCLC who underwent radical surgery. Tissue microarrays were constructed including tumor center (TC) and invasion margin (IM), and CK/CD4/CD8/PD-L1/programmed death-1 (PD-1) was labeled using multiplex immunofluorescence to decipher the counts and spatial distribution of tumor cells and T cells. The immune microenvironment and recurrence stratification were characterized using the Mann-Whitney U test and Cox proportional hazards model.

Result: Compared with the IM, the proportion of tumor cells (especially PD-L1⁺) was increased in the TC, while T cells (especially PD-1⁺) were decreased. An increase in TC PD-1⁺ CD8 T cells promoted relapse (HR = 2.183), while PD-L1⁺ tumor cells alone or in combination with T cells had no predictive value for relapse. In addition, in both TC and IM, CD8 were on average closer to PD-L1⁺ tumor cells than CD4, especially exhausted CD8. The effective density and percentage of PD-1⁺ CD4 T cells interacting with PD-L1⁺ tumor cells in the IM were both associated with recurrence, and the HRs increased sequentially (HRs were 2.809 and 4.063, respectively). Patients with low PD-1⁺CD4 count combined high PD-1⁺CD4 effective density showed significantly poorer RFS compared to those with high PD-1⁺CD4 count combined low PD-1⁺CD4 effective density, in both the TC and IM regions (HRs were 5.810 and 8.709, respectively).

Conclusion: Assessing the relative spatial proximity of PD-1/PD-L1 contributes to a deeper understanding of tumor immune escape and generates prognostic information in locally advanced NSCLC patients.

Keywords: Non-small cell lung cancer; Prognosis; Programmed death-1; Programmed death-ligand 1; Spatial interaction.