Immunological impact of tumor-draining lymph node dissection on systemic Th1-like CD4+ T cells in patients with early-stage lung cancer.

Introduction: Tumor-draining lymph nodes (LNs) are critical for initiating and maintaining antitumor immunity. However, systematic LN dissection (LND) remains the standard surgical procedure for lung cancer. This study aimed to investigate the immunological impact of tumor-draining LND on systemic T cell subsets.

Methods: We prospectively analyzed perioperative peripheral blood and resected LN samples from patients with early-stage lung adenocarcinoma who underwent lobectomy with systematic LND (systematic LND group) or wedge resection without LND (LN-preserving group). Perioperative immune cell dynamics were comprehensively profiled using mass cytometry.

Results: Unlike conventional CD4⁺ and CD8⁺ T cell subsets, Th7R (CXCR3^±CCR4^-CCR6⁺ CD62L^lowCD4⁺ T cell), a Th1-like CD4⁺ T cell cluster essential for antitumor immunity, consistently decreased in peripheral blood after tumor resection in both groups (p = 0.0016 and p = 0.0033). This decline was significantly milder in the LN-preserving group than in the systematic LND group (p = 0.0153). In LN analyses, Th7R percentages were significantly higher in hilar, interlobar, and peripheral LNs than in subcarinal and other mediastinal LNs (p = 0.0148). Th7R percentages in resected LNs strongly and negatively correlated with postoperative changes in peripheral blood (r = -0.857, p = 0.0137). Furthermore, greater declines in Th7R in peripheral blood were associated with postoperative oncological disease events.

Conclusions: Preserving LNs contributes to maintaining systemic antitumor immunity after surgery for early-stage lung cancer. Hilar, interlobar, and peripheral LNs may serve as primary reservoirs and supply sources of Th7R. In early-stage disease, these findings suggest a potential immunological benefit of LN-preserving strategies.