作者
Parth Desai, Nobuyuki Takahashi, Rajesh Kumar, Samantha Nichols, Justin Malin, Allison Hunt, Christopher Schultz, Yingying Cao, Desiree Tillo, Darryl Nousome, Lakshya Chauhan, Linda Sciuto, Kimberly Jordan, Vinodh Rajapakse, Mayank Tandon, Delphine Lissa, Yang Zhang, Suresh Kumar, Lorinc Pongor, Abhay Singh, Brett Schroder, Ajit Kumar Sharma, Tiangen Chang, Rasa Vilimas, Danielle Pinkiert, Chante Graham, Donna Butcher, Andrew Warner, Robin Sebastian, Mimi Mahon, Karen Baker, Jennifer Cheng, Ann Berger, Ross Lake, Melissa Abel, Manan Krishnamurthy, George Chrisafis, Peter Fitzgerald, Micheal Nirula, Shubhank Goyal, Devon Atkinson, Nicholas W Bateman, Tamara Abulez, Govind Nair, Andrea Apolo, Udayan Guha, Baktiar Karim, Rajaa El Meskini, Zoe Weaver Ohler, Mohit Kumar Jolly, Alejandro Schaffer, Eytan Ruppin, David Kleiner, Markku Miettinen, G Tom Brown, Stephen Hewitt, Thomas Conrads, Anish Thomas
发表日期
2024/6/18
期刊
Cell Reports Medicine
卷号
5
期号
6
出版商
Elsevier
简介
Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic 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 TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME …
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P Desai, N Takahashi, R Kumar, S Nichols, J Malin… - Cell Reports Medicine, 2024