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Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.
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 Weaver; Jolly, Mohit Kumar.
Affiliation
  • Desai P; 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.
  • Takahashi N; 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.
  • Kumar R; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Nichols S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Malin J; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Hunt A; Women's Health Integrated Research Center, Inova Health System, Falls Church, VA, USA.
  • Schultz C; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Cao Y; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Tillo D; CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Nousome D; CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chauhan L; Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
  • Sciuto L; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Jordan K; Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Rajapakse V; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Tandon M; CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Lissa D; Laboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Zhang Y; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Kumar S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Pongor L; HCEMM Cancer Genomics and Epigenetics Research Group, Szeged, Hungary.
  • Singh A; Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
  • Schroder B; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Sharma AK; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chang T; Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Vilimas R; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Pinkiert D; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Graham C; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Butcher D; Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • Warner A; Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • Sebastian R; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Mahon M; Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Baker K; Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Cheng J; Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Berger A; Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
  • Lake R; Laboratory of Genitourinary cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Abel M; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Krishnamurthy M; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chrisafis G; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Fitzgerald P; CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Nirula M; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Goyal S; Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Atkinson D; Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • Bateman NW; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.
  • Abulez T; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.
  • Nair G; National Institute of Neurological Disorders and Stroke, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Apolo A; Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Guha U; Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Karim B; Molecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • El Meskini R; Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • Ohler ZW; Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
  • Jolly MK; Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
Cell Rep Med ; 5(6): 101610, 2024 Jun 18.
Article in En | MEDLINE | ID: mdl-38897168
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Small Cell Lung Carcinoma / Tumor Microenvironment / Lung Neoplasms Limits: Female / Humans / Male Language: En Journal: Cell Rep Med Year: 2024 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Small Cell Lung Carcinoma / Tumor Microenvironment / Lung Neoplasms Limits: Female / Humans / Male Language: En Journal: Cell Rep Med Year: 2024 Type: Article Affiliation country: United States