140P - Mining metastatic lymph nodes for response to immune checkpoint therapy in non-small cell lung cancer

Background

Tumor-draining lymph nodes are a potent source of antitumor immunity. Upon tumoral invasion, however, progressive immune dysfunction may occur. Whether the composition of metastatic lymph nodes (mLN) can influence or even predict response to immunotherapy remains unclear. This question is especially relevant in advanced non-small cell lung cancer (NSCLC), where the primary tumor is often not accessible for sampling and mLN serve as a substitute to guide immune checkpoint blockade therapy (ICB). Profiling both compartments, we aim to contribute to a better understanding of the NSCLC tumor microenvironment and improve available predictive biomarkers for ICB response.

Methods

Tumor (N=15) and mLN (N=31) samples of 46 treatment-naive advanced NSCLC patients were subjected to single-cell RNA sequencing. For 26 patients, the molecular findings were correlated with durable response to anti-PD-1 backbone therapy.

Results

In this preliminary analysis, we compare the microenvironment of mLN and primary tumor. In total 281,707 cells were recovered for analysis. At major cell type level, mLN house significantly more B cells and monocytes. Plasma cells and macrophages are more abundant at the primary tumor site. Neutrophil abundance is comparable between compartments. For T cells, we see a trend towards enrichment in mLN, albeit not significant. At subtype level, CD4+ naive, follicular helper and regulatory T cells are enriched in mLN, whilst CD4+ T helper 1, CD8+ terminal effector memory and resident memory T cells are more abundant at the primary tumor site. The proportion of exhausted CD8+ T cells does not differ significantly between the two compartments. Predictive analysis is ongoing.

Conclusions

Despite tumoral invasion, the lymph node microenvironment of NSCLC remains more naive, reflective of its native priming function. Interestingly, however, exhausted T cells are not restricted to the primary tumor. How this influences response to ICB remains to be investigated.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

KU Leuven – VIB.

Funding

VIB - KU Leuven; Leerstoel MD Davidse beheer immunologie; FWO Vlaanderen; Stichting Tegen Kanker.

Disclosure

The author has declared no conflicts of interest.