Abstract
CD8+ tissue-resident memory T cells (CD8+TRM), expressing PD-1 and/or TIM-3, are linked to immunological surveillance in non-small cell lung cancer (NSCLC). However, their prognostic value across activation states and spatial distributions in NSCLC stages is unclear. We analyzed 271 NSCLC patients' primary tumors and lymph nodes, using multiplex immunohistochemistry and inForm software for cell identification. Statistical analyses included the Mann-Whitney U test and Cox survival analysis. Findings showed CD8+TRM were categorized into four activation states. In locally advanced NSCLC, PD-1-TIM-3+CD8+TRM3, and PD-1+TIM-3+CD8+TRM4 densities were notably higher at invasive margins. Fewer interactions between CD8+TRM and tumor cells were observed in advanced lesions. Decreased PD-1+TIM-3-CD8+TRM2 interactions with tumor cells and increased PD-1+TIM-3+CD8+TRM4 interactions with tumor cells were independently associated with recurrence in patients with early lung adenocarcinoma and squamous carcinoma, respectively. These results suggest that CD8+TRM activation state and distribution are linked to recurrence risk in early-stage NSCLC, emphasizing the importance of CD8+TRM spatial dynamics in prognosis.