The Tumor Immune Microenvironment Is Associated with Recurrence in Early-Stage Lung Adenocarcinoma

Introduction Immune checkpoint inhibitors have recently been approved for treatment of early-stage non–small cell lung cancer (NSCLC) in the perioperative setting based on phase 3 trials. However, the characteristics of such patients who are prone to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed cell death–ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes (TILs), and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ TIL density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis. Results A total of 117 patients was included in this study. Median RFS was not reached (95% CI, 22.4 months–not reached; n = 39) and 23.7 months (95% CI, 14.5–43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, HR of 0.52 [95% CI, 0.29–0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify early-stage NSCLC patients susceptible to recurrence after adjuvant chemotherapy.