WCLC 2025 - Posters & ePosters-EP.13.48 Natural Killer (NK) Cell Heterogeneity in Small Cell Lung Cancer: Implications for Chemo-Immunotherapy Response

EP.13.48 Natural Killer (NK) Cell Heterogeneity in Small Cell Lung Cancer: Implications for Chemo-Immunotherapy Response

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This study investigates the heterogeneity of Natural Killer (NK) cells in Small Cell Lung Cancer (SCLC) and its impact on chemo-immunotherapy response. SCLC is an aggressive cancer with poor survival, and while immunotherapy shows promise, only a subset of patients benefits. The research aimed to link NK cell diversity to treatment outcomes, focusing on the effects of cisplatin chemotherapy on NK cell function.<br /><br />A cohort of 20 SCLC patients was categorized into Best Responders (BR) and Non-Responders (NR) based on progression-free survival. Peripheral blood mononuclear cells (PBMCs) were collected to enrich NK cells, which were then analyzed via bulk RNA sequencing, flow cytometry, single-cell sorting, and multiplex cytokine assays. Key findings showed that BR patients’ NK cells displayed enriched cytotoxic subtypes NK3 and NK1B, with higher expression of cytolytic molecules such as granzyme A (GZMA), granzyme B (GZMB), perforin (PRF1), and interferon (IFN). These NK cells also upregulated pathways related to interferon response and DNA repair, while NR patients’ NK cells showed widespread downregulation of these pathways.<br /><br />Quantitative analyses revealed a significantly higher proportion of NK1 cells and a dominant presence of NK3 subsets in BR patients compared to NR. Notably, cisplatin treatment further enhanced the functional activity of NK cells in BR patients by increasing the release of key cytotoxic molecules.<br /><br />The study concludes that NK cell diversity critically shapes treatment efficacy in SCLC, with cytotoxic NK subsets linked to better responses. Cisplatin not only acts directly on cancer cells but also potentiates NK cell function. These findings suggest that NK cell signatures could serve as biomarkers for patient stratification and therapy optimization. Future research should validate these biomarkers in larger cohorts, explore NK-targeted therapies to boost immunotherapy, and incorporate NK profiling into clinical decision-making tools.

Asset Subtitle

Caterina De Rosa

Meta Tag

Speaker Caterina De Rosa

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

Natural Killer cells

Small Cell Lung Cancer

SCLC

chemo-immunotherapy response

cisplatin chemotherapy

NK cell heterogeneity

cytotoxic NK subsets

granzyme A

granzyme B

patient stratification biomarkers