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

Abstract

Tumor metastasis significantly impacts the prognosis of non-small cell lung cancer (NSCLC) patients,with lymph node (LN) metastasis being the most common and early form of spread. With the development ofadjuvant immunotherapy, increasing attention has been paid to the tumor-draining lymph nodes（TDLN) in early-stageNSCLC, especially tumor-metastatic lymph nodes, which provides poor prognostic information but haspotential benefits in adjuvant treatment. We showed the remodeled immune environment in TDLNs through using TCR-seq to analyse 24 primarylung cancer tissues and 134 LNs from 24 lung cancer patients with or without LN metastasis. Additionally, wecharacterized the spatial profiling of immunocytes and tumor cells in TDLNs and primary tumor sites through usingmulti-IHC. We found the remodeled immune environment in TDLNs through analyzing primary lung cancer tissuesand LNs from NSCLC patients with or without LN metastasis. Considering the intricate communication betweentumor and immunocytes, we further subdivided TDLNs, revealing that metastasis-negative LNs from LN-metastaticpatients (MNLN) exhibited greater immune activation, exhaustion, and memory in comparison to both metastasis-positiveLNs (MPLN) and TDLNs from non-LN-metastatic patients (NMLN). Our data indicate that LN metastasis facilitated tumor-specific antigen presentation in TDLNs andinduces T cell priming, while existing tumor cells generate an immune-suppressive environment in MPLNs throughmultiple mechanisms. These findings contribute to a comprehensive understanding of the immunologicalmechanisms through which LN metastasis influences tumor progression and plays a role in immunotherapy forNSCLC patients.