2023 World Conference on Lung Cancer (Posters)-P2.15. Priming SCLC Vasculature to Facilitate NK Cell Attack

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The document is a research article titled "Priming SCLC vasculature to facilitate NK cell attack" published in Cancer Discovery in 2021. The study aims to develop a novel 3-dimensional microphysiological system (MPS) to study the tumor microenvironment (TME) and predict treatment response in real time. The researchers focus on small cell lung carcinoma (SCLC) and its vulnerability to natural killer (NK) cell-mediated cytotoxicity.<br /><br />The study uses single-cell RNA sequencing to analyze the effect of cGAS-STING agonism on the TME components, such as endothelial cells, fibroblasts, and SCLC cells. They find that neuroendocrine SCLC subpopulations, which downregulate MHC Class I expression, are vulnerable to NK cell therapies. The researchers also develop a 3D microfluidic model of the TME to examine the sensitivity of MHC I-low and MHC I-high SCLC cells to NK cell attack. They find that priming the SCLC vasculature enhances NK cell infiltration and cytotoxicity.<br /><br />The study demonstrates that stromal cells, including endothelial cells and fibroblasts, respond to STING agonism by promoting NK cell extravasation and recruitment. The researchers also observe an inert immunologic phenotype in neuroendocrine MHC I-low SCLC, characterized by decreased production of chemotactic factors and a cold immune desert microenvironment. The MPS system allows the researchers to recapitulate time biology and study immune infiltration and killing in the TME.<br /><br />Overall, the research provides insights into the immunogenicity of small cell lung carcinoma and suggests that priming the vasculature can enhance NK cell-mediated cytotoxicity. The novel MPS system offers a platform for studying immune therapies and identifying therapeutic vulnerabilities in the tumor microenvironment.

Asset Subtitle

Navin Mahadevan

Meta Tag

Speaker Navin Mahadevan

Topic SCLC & Neuroendocrine Tumors: Preclinical

Keywords

Priming SCLC vasculature

NK cell attack

3-dimensional microphysiological system

tumor microenvironment

small cell lung carcinoma

MHC Class I expression

NK cell therapies

MHC I-low SCLC cells

STING agonism

MPS system