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Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities

  1. Author:
    Desai, Parth
    Takahashi, Nobuyuki
    Kumar, Rajesh
    Nichols, Samantha
    Malin, Justin
    Hunt, Allison
    Schultz, Christopher
    Cao, Yingying
    Tillo, Desiree
    Nousome, Darryl
    Chauhan, Lakshya
    Sciuto, Linda
    Jordan, Kimberly
    Rajapakse, Vinodh
    Tandon, Mayank
    Lissa, Delphine
    Zhang, Yang
    Kumar, Suresh
    Pongor, Lorinc
    Singh, Abhay
    Schroder, Brett
    Sharma, Ajit Kumar
    Chang, Tiangen
    Vilimas, Rasa
    Pinkiert, Danielle
    Graham, Chante
    Butcher,Donna
    Warner,Andrew
    Sebastian, Robin
    Mahon, Mimi
    Baker, Karen
    Cheng, Jennifer
    Berger, Ann
    Lake, Ross
    Abel, Melissa
    Krishnamurthy, Manan
    Chrisafis, George
    Fitzgerald, Peter
    Nirula, Micheal
    Goyal, Shubhank
    Atkinson, Devon
    Bateman, Nicholas W
    Abulez, Tamara
    Nair, Govind
    Apolo, Andrea
    Guha, Udayan
    Karim,Baktiar
    El Meskini,Rajaa
    Ohler,Zoe
    Jolly, Mohit Kumar
    Schaffer, Alejandro
    Ruppin, Eytan
    Kleiner, David
    Miettinen, Markku
    Brown, G Tom
    Hewitt, Stephen
    Conrads, Thomas
    Thomas, Anish

  2. Author Address

    Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medical Oncology, Fox Chase Cancer Center, Temple University Hospital and Lewis Katz School of Medicine, Philadelphia, PA, USA., Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Women 39;s Health Integrated Research Center, Inova Health System, Falls Church, VA, USA., Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India., Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Laboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., HCEMM Cancer Genomics and Epigenetics Research Group, Szeged, Hungary., Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA., Laboratory of Genitourinary cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA., National Institute of Neurological Disorders and Stroke, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: anish.thomas@nih.gov.,
    1. Year: 2024
    2. Date: Jun 18
  2. Journal: Cell Reports. Medicine
    1. 5
    2. 6
    3. Pages: 101610
  4. Type of Article: Article
  5. Article Number: 101610
  1. Abstract:

    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 ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.xcrm.2024.101610
  3. PMID: 38897168
  4. PII : S2666-3791(24)00314-8

Library Notes

  1. Fiscal Year: FY2023-2024
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