Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Immune Environment in Glioblastoma (Upcoming)
    • Korsmeyer Award 25th Anniversary Collection (Jan 2023)
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Research letters
    • Letters to the editor
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Research letters
  • Letters to the editor
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers
Tina Gruosso, … , Benjamin Haibe-Kains, Morag Park
Tina Gruosso, … , Benjamin Haibe-Kains, Morag Park
Published February 12, 2019
Citation Information: J Clin Invest. 2019;129(4):1785-1800. https://doi.org/10.1172/JCI96313.
View: Text | PDF
Research Article Oncology

Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers

  • Text
  • PDF
Abstract

Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC, with implications for current therapies including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+CD8+ T cells (GzmB+CD8+ T cells), a type 1 IFN signature, and elevated expression of multiple immune inhibitory molecules including indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1), and resulted in good outcomes. An “immune-cold” microenvironment with an absence of tumoral CD8+ T cells was defined by elevated expression of the immunosuppressive marker B7-H4, signatures of fibrotic stroma, and poor outcomes. A distinct poor-outcome immunomodulatory microenvironment, hitherto poorly characterized, exhibited stromal restriction of CD8+ T cells, stromal expression of PD-L1, and enrichment for signatures of cholesterol biosynthesis. Metasignatures defining these TIME subtypes allowed us to stratify TNBCs, predict outcomes, and identify potential therapeutic targets for TNBC.

Authors

Tina Gruosso, Mathieu Gigoux, Venkata Satya Kumar Manem, Nicholas Bertos, Dongmei Zuo, Irina Perlitch, Sadiq Mehdi Ismail Saleh, Hong Zhao, Margarita Souleimanova, Radia Marie Johnson, Anne Monette, Valentina Muñoz Ramos, Michael Trevor Hallett, John Stagg, Réjean Lapointe, Atilla Omeroglu, Sarkis Meterissian, Laurence Buisseret, Gert Van den Eynden, Roberto Salgado, Marie-Christine Guiot, Benjamin Haibe-Kains, Morag Park

×

Figure 5

Tumors with poor infiltration of CD8+ T cells are enriched for fibrotic foci.

Options: View larger image (or click on image) Download as PowerPoint
Tumors with poor infiltration of CD8+ T cells are enriched for fibrotic ...
(A) Representative image of fibrotic focus in H&E-stained images. Original image size: 7 × 10 mm; enlarged inset size: 0.5 × 0.5 mm. Dotted line identifies the fibrotic focus area. (B) Fibrotic focus presence represented as a 2D plot of marCD8 over corCD8 densities (n = 38). (C) Fibrotic focus presence was enriched in corCD8lo compared with corCD8hi tumors (n = 38). Data were analyzed using the Fisher’s exact test. (D) corCD8 was higher in tumors that did not contain a fibrotic focus (n = 38). Data were analyzed using the Mann-Whitney U test. Data represent the mean ± SEM.

Copyright © 2023 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts