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

Tumor Microenvironment Humans Small Cell Lung Carcinoma / pathology Lung Neoplasms / pathology Cancer-Associated Fibroblasts / metabolism Neuroendocrine Tumors / pathology Neuroendocrine Cells / pathology Female Male Prognosis
cancer-associated fibroblasts intercellular communication rapid research autopsy small-cell lung cancer spatial transcriptomics tumor heterogeneity tumor microenvironment

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
18 Jun 2024
Historique:
received: 02 03 2023
revised: 04 08 2023
accepted: 17 05 2024
medline: 20 6 2024
pubmed: 20 6 2024
entrez: 19 6 2024
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.xcrm.2024.101610 PMID: 38897168
pubmed: 38897168
pii: S2666-3791(24)00314-8
doi: 10.1016/j.xcrm.2024.101610
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

101610

Informations de copyright

Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interests A.T. received grants to NCI from EMD Serono Research & Development, AstraZeneca, Gilead Sciences, and ProLynx during the conduct of the study.

Auteurs

Parth 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.

Nobuyuki 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.

Rajesh Kumar (R)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Samantha Nichols (S)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Justin Malin (J)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Allison Hunt (A)

Women's Health Integrated Research Center, Inova Health System, Falls Church, VA, USA.

Christopher Schultz (C)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Yingying Cao (Y)

Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Desiree Tillo (D)

CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Darryl Nousome (D)

CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Lakshya Chauhan (L)

Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.

Linda Sciuto (L)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Kimberly Jordan (K)

Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Vinodh Rajapakse (V)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Mayank Tandon (M)

CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Delphine Lissa (D)

Laboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Yang Zhang (Y)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Suresh Kumar (S)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Lorinc Pongor (L)

HCEMM Cancer Genomics and Epigenetics Research Group, Szeged, Hungary.

Abhay Singh (A)

Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.

Brett Schroder (B)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Ajit Kumar Sharma (AK)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Tiangen Chang (T)

Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Rasa Vilimas (R)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Danielle Pinkiert (D)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Chante Graham (C)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Donna 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.

Andrew 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.

Robin Sebastian (R)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Mimi Mahon (M)

Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.

Karen Baker (K)

Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.

Jennifer Cheng (J)

Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.

Ann Berger (A)

Pain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.

Ross Lake (R)

Laboratory of Genitourinary cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Melissa Abel (M)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Manan Krishnamurthy (M)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

George Chrisafis (G)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Peter Fitzgerald (P)

CCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Micheal Nirula (M)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Shubhank Goyal (S)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Devon Atkinson (D)

Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Nicholas W Bateman (NW)

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Tamara Abulez (T)

The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.

Govind Nair (G)

National Institute of Neurological Disorders and Stroke, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Andrea Apolo (A)

Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Udayan Guha (U)

Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Baktiar 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.

Rajaa El Meskini (R)

Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Zoe Weaver Ohler (ZW)

Center for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.

Mohit Kumar Jolly (MK)

Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.

Alejandro Schaffer (A)

Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Eytan Ruppin (E)

Cancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

David Kleiner (D)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Markku Miettinen (M)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

G Tom Brown (GT)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Stephen Hewitt (S)

Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Thomas Conrads (T)

Women's Health Integrated Research Center, Inova Health System, Falls Church, VA, USA.

Anish Thomas (A)

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: anish.thomas@nih.gov.

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Tumeurs des bronches › Carcinome bronchogénique › Carcinome pulmonaire à petites cellules › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Tumeurs de l'appareil respiratoire › Tumeurs du poumon › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Fibroblastes associés au cancer › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroendocrines › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Cellules › Cellules endocrines › Cellules neuroendocrines › Microenvironment shapes small-cell lung cancer...
questionsmedicales.fr › Diagnostic › Pronostic › Microenvironment shapes small-cell lung cancer...