Improved Genetic Models for Non-small-cell Lung Cancer

Cell fate lineage specifiers that determine lung tumor subtype (SOX2 and NKX2-1) control the tumor immune microenvironment by opposing CXCL5, a neutrophil recruitment chemokine.

The major types of non-small-cell lung cancers (squamous cell carcinoma and adenocarcinoma) have unique mutational drivers, that result in tumors with distinct immune microenvironments. Issues of high interest include identifying the transcription factors that determine the differences between squamous cell carcinoma and adenocarcinoma, and whether and how these two tumor types interact with and impact the immune system. To address this issue, Oliver and colleagues developed a genetic model of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and used the model to show how lineage-defining transcription factors such as Sox2 and NKX2-1 activate genes and pathways that determine different tumor immune microenvironments.

Trudy Oliver, PhD


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The lineage-defining transcription factors SOX2 and NKX2-1 determine lung cancer cell fate and shape the tumor immune microenvironment. Mollaoglu G, Jones A, Wait SJ, Mukhopadhyay A, Jeong S, Arya R, Camolotto SA, Mosbruger TL, Stubben CJ, Conley CJ, Bhutkar A, Vahrenkamp JM, Berrett KC, Cessna MH, Lane TE, Witt BL, Salama ME, Gertz J, Jones KB, Snyder EL, Oliver TG. Immunity. 2018 Oct;49(4):764.

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