Integration of TRM-Cell Infiltration and PD-L1 Expression Improves Prognostic Stratification After Resection of NSCLC

Background/Aim: Tumor-infiltrating lymphocytes, including tissue-resident memory T (TRM) cells, are associated with prognosis in patients after resection of non-small-cell lung cancer (NSCLC). However, their clinical significance in the context of tumor immune suppression, such as through expression of programmed cell death ligand-1 (PD-L1), remains unclear. We hypothesized that integrating TRM-cell infiltration with PD-L1 expression would improve prognostic stratification. Patients and Methods: We retrospectively analyzed 316 patients with NSCLC who underwent curative resection between 2017 and 2020 without perioperative immunotherapy. TRM cells were quantified by CD103 immunohistochemistry using tissue microarrays and digitally analyzed with QuPath. PD-L1 expression was assessed using the 22C3 assay. Recurrence was evaluated using competing-risks analysis. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards models. Results: The median TRM density was 54.8 cells/mm2 and was used to define TRM-high and TRM-low groups. TRM-high tumors were associated with non-adenocarcinoma histology and PD-L1 expression ≥1%. Patients with TRM-high tumors showed a significantly lower cumulative incidence of recurrence (p=0.039), whereas PD-L1 expression ≥1% was associated with worse RFS and OS. When combined, TRM-high/PD-L1 expression <1% demonstrated lowest cumulative incidence of recurrence (p=0.017) and significantly improved RFS and OS (p=0.0035 and p=0.0031, respectively). In multivariable analysis, TRM-high/PD-L1 expression <1% was independently associated with lower recurrence (hazard ratio=0.36) and improved RFS (hazard ratio=0.47). Conclusion: The combined assessment of TRM-cell infiltration and PD-L1 expression provides robust prognostic stratification in resected NSCLC and may serve as a useful biomarker for predicting postoperative outcomes.