Immune characteristics associated with lymph node metastasis in early-stage NSCLC

Abstract Tumor metastasis is one of the important reasons for the poor prognosis of non-small cell lung cancer (NSCLC) patients, in which lymph node (LN) metastasis is the earliest and most frequent metastasis. With the development of adjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes（TDLN）in early-stage NSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but has potential benefits in adjuvant treatment. Here, we showed the remodeled immune environment in TDLNs through using TCR-seq and multi-IHC to analyze primary lung cancer tissues and LNs from NSCLC patients with or without LN metastasis. Considering the complex communication between tumor and immunocytes, we subdivided TDLNs and found that metastasis-negative LNs from LN-metastatic patients (MNLN) exhibit more immune activation, exhaustion, and memory compared with both metastasis-positive LNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN). LN metastasis promotes tumor-specific antigen presentation in TDLNs and induces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs through multiple ways. The evidence implicates the comprehensive immunological mechanism by which LN metastasis influences tumor progression and plays a role in immunotherapy in NSCLC patients.