Higher lymph node yield is associated with increased postoperative recurrence in colorectal cancer treated with neoadjuvant immunotherapy: a retrospective cohort study

Tumor-draining lymph nodes (TDLNs) play a critical role in mediating responses to immune checkpoint inhibitors (ICI). However, the impact of extensive TDLN yield on survival outcomes in colorectal cancer (CRC) patients undergoing neoadjuvant immunotherapy remains unclear. This study aims to investigate the influence of the number of TDLNs dissected on recurrence-free survival (RFS) in CRC patients treated with neoadjuvant immunotherapy, with a particular focus on elucidating the role of TDLNs in immune responses to ICI. We retrospectively analyzed data from 195 CRC patients who underwent curative surgery following neoadjuvant ICI therapy. The study assessed the number of lymph node yield and its association with postoperative recurrence. Single-cell RNA sequencing and T-cell receptor sequencing were conducted on tumor, peripheral blood, and TDLN samples from CRC patients. Our findings revealed that higher lymph node yield (≥ 20 nodes) was associated with poorer RFS in TNdiss CRC patients treated with ICI. Single-cell analysis showed ICI‑treated patients exhibited a higher frequency of clonally shared CD8 + Tem cells between TDLNs and tumor tissues, suggesting immunological connectivity between these compartments. A higher lymph node yield was associated with poorer survival outcomes in CRC patients receiving neoadjuvant immunotherapy. However, the mechanisms underlying this association remain unclear and warrant further investigation.