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Microenvironment Shapes Small Cell Lung Cancer Neuroendocrine States and Presents Unique Therapeutic Opportunities

ABSTRACT: Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting an exceptionally poor prognosis. Together, our work provides the first comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell, Stromal Cell

DISEASE(S): Lung Small Cell Carcinoma

SUBMITTER: Thomas Conrads

LAB HEAD: Thomas P. Conrads, PhD

PROVIDER: PXD052033 | Pride | 2024-05-15

REPOSITORIES: Pride

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			Action	DRS
	Human_SP_120117.fasta	Fasta
	NCI_SCLC_Sample_Reference_File_v1.xlsx	Xlsx
	NCI_SCLC_TMTpro18_QEHFX3_072722_1_01.raw	Raw
	NCI_SCLC_TMTpro18_QEHFX3_072722_1_02.raw	Raw
	NCI_SCLC_TMTpro18_QEHFX3_072722_1_03.raw	Raw

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