2024 World Conference on Lung Cancer (WCLC) - Posters-P4.07E.08 Single-Cell TCR Barcoding and RNA Sequencing Illuminate Distinct Tumor-Draining Lymph Node T Cell Responses to Neoadjuvant PD-1 Blockade

P4.07E.08 Single-Cell TCR Barcoding and RNA Sequencing Illuminate Distinct Tumor-Draining Lymph Node T Cell Responses to Neoadjuvant PD-1 Blockade

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This study investigates the response of T cells from tumor-draining lymph nodes (tdLNs) to neoadjuvant PD-1 blockade in the context of surgically resected non-small-cell lung cancer (NSCLC). Utilizing single-cell RNA sequencing and TCR barcoding, the researchers conducted a multi-tissue deep clonal tracking to unravel the dynamics of CD8 T cells within tumors and tdLNs.<br /><br />The central focus was to understand the role of tdLN-derived T cells in mediating the response to PD-1 immune checkpoint inhibitors. The study highlights a unique response by T cells from tdLNs when exposed to PD-1 blockade therapy. These T cells were enriched in memory-like genes, while tumor-infiltrating T cells exhibited enrichment in cytotoxic and exhaustion markers like TOX and PDCD1.<br /><br />The study used unsupervised machine learning techniques to distinguish between different T-cell subtypes, identifying clusters such as memory-like, effector, and exhausted-like T cells. It found that tdLN-derived T cells were generally more quiescent and less terminally differentiated compared to their tumor-infiltrating counterparts.<br /><br />Upon treatment with PD-1 blockade, both tdLN and tumor-associated T cells exhibited increased cytotoxicity and elevated granzyme expression. These findings suggest that tdLN-derived T cells could play a significant role in shaping the tumor's response to PD-1 blockade therapy by providing a reservoir of memory-like cells that can differentiate upon treatment.<br /><br />The study provides a deeper molecular understanding of T-cell responses in tdLNs and tumors, offering insights into how immune checkpoint therapies like PD-1 blockade initiate antitumor responses. The research could possibly inform future strategies to improve the effectiveness of immunotherapies in NSCLC and other types of cancer by leveraging the distinct characteristics of tdLN-derived T cells.

Asset Subtitle

Rachel Honigsberg

Meta Tag

Speaker Rachel Honigsberg

Topic Early-Stage NSCLC

Keywords

T cells

tumor-draining lymph nodes

neoadjuvant PD-1 blockade

non-small-cell lung cancer

single-cell RNA sequencing

TCR barcoding

immune checkpoint inhibitors

memory-like genes

cytotoxicity

immunotherapy