[The impact of CD8+ memory and bystander T cells on the prognosis of non-small cell lung cancer].

Objectives: To investigate the relationship between CD8+ tissue-resident memory T cells (TRM) and CD8+ bystander T cells (Tbys) in the tumor center (TC) and invasive margin (IM) regions of primary non-small cell lung cancer (NSCLC) and recurrence, and to perform stratified analysis based on lymph node status to guide individualized treatment. Methods: A retrospective review was conducted of patients with stage IA-IIIB non-small cell lung cancer (NSCLC) who underwent radical surgery at Shandong Provincial Cancer Hospital between January 1, 2014 and December 31, 2018. Tissue microarrays containing TC and IM regions were prepared, and multicolor immunofluorescence staining was applied to quantify the density of CD8+ T cells (CK- CD8+), tissue-resident memory T cells (CK- CD103+ CD8+), and bystander T cells (CK- CD103- CD8+). Kaplan-Meier and Cox proportional hazards models were used to identify factors associated with recurrence. Results: In the TC region, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys accounted for 34.3%, 67.9%, and 50.5% of CD8+ T cells, respectively. In the IM region, TRM/CD8+ T cells accounted for 29.6%, Tbys/CD8+ T cells for 70.7%, and TRM/Tbys for 41.9%. At a median follow-up of 37.9 months, recurrence occurred in 87 patients (34.0%). In all 256 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in both IM and TC regions were unrelated to RFS (all P＞0.05). Among the 172 N0 patients, the high Tbys/CD8+ T cell group in the IM region showed higher RFS rates than the low group (P=0.050), while the high-level groups for TRM/CD8+ T cells and TRM/Tbys in the TC region showed lower RFS rates than their low-level counterparts (all P＜0.05). Conversely, the high-level group for Tbys/CD8+ T cells in the TC region demonstrated a higher RFS rate than the low-level group (P=0.005). Multivariate Cox analysis revealed that high TC TRM/CD8+ T cells and high TC TRM/Tbys were independent risk factors for postoperative recurrence in N0 NSCLC patients (HR=2.772, 95% CI: 1.260-6.098; HR=2.656, 95% CI: 1.205-5.855), while high TC Tbys/CD8+ T cells was an independent protective factor for postoperative recurrence in N0 NSCLC patients (HR=0.324, 95% CI: 0.147-0.711). Among the 84 N1-2 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in the IM and TC regions were not associated with RFS (all P＞0.05). Conclusions: Specific CD8+ T cell subsets in the TC region of the primary tumor in NSCLC patients are associated only with recurrence after curative surgery in N0 patients. Elevated TRM/CD8+ T and TRM/Tbys ratios, coupled with reduced Tbys/CD8+ T ratios, correlate with heightened recurrence risk. This may aid in stratifying the risk of recurrence in N0 patients after surgery and guide treatment strategies.