IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development
Summary: Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown....
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-12-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314536 |
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doaj-23e127cdd30c49738de5fb370ca4ae6d |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Amy Li Rebecca H. Herbst David Canner Jason M. Schenkel Olivia C. Smith Jonathan Y. Kim Michelle Hillman Arjun Bhutkar Michael S. Cuoco C. Garrett Rappazzo Patricia Rogers Celeste Dang Livnat Jerby-Arnon Orit Rozenblatt-Rosen Le Cong Michael Birnbaum Aviv Regev Tyler Jacks |
| spellingShingle |
Amy Li Rebecca H. Herbst David Canner Jason M. Schenkel Olivia C. Smith Jonathan Y. Kim Michelle Hillman Arjun Bhutkar Michael S. Cuoco C. Garrett Rappazzo Patricia Rogers Celeste Dang Livnat Jerby-Arnon Orit Rozenblatt-Rosen Le Cong Michael Birnbaum Aviv Regev Tyler Jacks IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development Cell Reports |
| author_facet |
Amy Li Rebecca H. Herbst David Canner Jason M. Schenkel Olivia C. Smith Jonathan Y. Kim Michelle Hillman Arjun Bhutkar Michael S. Cuoco C. Garrett Rappazzo Patricia Rogers Celeste Dang Livnat Jerby-Arnon Orit Rozenblatt-Rosen Le Cong Michael Birnbaum Aviv Regev Tyler Jacks |
| author_sort |
Amy Li |
| title |
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development |
| title_short |
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development |
| title_full |
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development |
| title_fullStr |
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development |
| title_full_unstemmed |
IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor Development |
| title_sort |
il-33 signaling alters regulatory t cell diversity in support of tumor development |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2019-12-01 |
| description |
Summary: Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single-cell RNA sequencing (RNA-seq) to longitudinally profile dynamic shifts in the distribution of Tregs in a genetically engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive Tregs are more prevalent early in tumor development, whereas a specialized effector phenotype characterized by enhanced expression of the interleukin-33 receptor ST2 is predominant in advanced disease. Treg-specific deletion of ST2 alters the evolution of effector Treg diversity, increases infiltration of CD8+ T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention. : Li et al. show in a genetic mouse model of lung adenocarcinoma that during tumor development regulatory T cell (Treg) diversity shifts from an interferon-responsive to a ST2-positive, Klrg1+Areg+ effector-like phenotype. Treg-specific deletion of ST2 alters Treg heterogeneity, increases tumor infiltration by CD8+ T cells, and decreases tumor burden. Keywords: regulatory T cell, autochthonous mouse model of cancer, lung adenocarcinoma, tumor immunosuppression, single cell RNA sequencing, Treg heterogeneity, interleukin-33, ST2, Il1rl1 |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719314536 |
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doaj-23e127cdd30c49738de5fb370ca4ae6d2020-11-25T01:08:10ZengElsevierCell Reports2211-12472019-12-01291029983008.e8IL-33 Signaling Alters Regulatory T Cell Diversity in Support of Tumor DevelopmentAmy Li0Rebecca H. Herbst1David Canner2Jason M. Schenkel3Olivia C. Smith4Jonathan Y. Kim5Michelle Hillman6Arjun Bhutkar7Michael S. Cuoco8C. Garrett Rappazzo9Patricia Rogers10Celeste Dang11Livnat Jerby-Arnon12Orit Rozenblatt-Rosen13Le Cong14Michael Birnbaum15Aviv Regev16Tyler Jacks17David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USAHarvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USABroad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames Street, Cambridge, MA 02142, USABroad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USABroad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USABroad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USADepartment of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, 21 Ames Street, Cambridge, MA 02142, USADavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding authorDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding authorSummary: Regulatory T cells (Tregs) can impair anti-tumor immune responses and are associated with poor prognosis in multiple cancer types. Tregs in human tumors span diverse transcriptional states distinct from those of peripheral Tregs, but their contribution to tumor development remains unknown. Here, we use single-cell RNA sequencing (RNA-seq) to longitudinally profile dynamic shifts in the distribution of Tregs in a genetically engineered mouse model of lung adenocarcinoma. In this model, interferon-responsive Tregs are more prevalent early in tumor development, whereas a specialized effector phenotype characterized by enhanced expression of the interleukin-33 receptor ST2 is predominant in advanced disease. Treg-specific deletion of ST2 alters the evolution of effector Treg diversity, increases infiltration of CD8+ T cells into tumors, and decreases tumor burden. Our study shows that ST2 plays a critical role in Treg-mediated immunosuppression in cancer, highlighting potential paths for therapeutic intervention. : Li et al. show in a genetic mouse model of lung adenocarcinoma that during tumor development regulatory T cell (Treg) diversity shifts from an interferon-responsive to a ST2-positive, Klrg1+Areg+ effector-like phenotype. Treg-specific deletion of ST2 alters Treg heterogeneity, increases tumor infiltration by CD8+ T cells, and decreases tumor burden. Keywords: regulatory T cell, autochthonous mouse model of cancer, lung adenocarcinoma, tumor immunosuppression, single cell RNA sequencing, Treg heterogeneity, interleukin-33, ST2, Il1rl1http://www.sciencedirect.com/science/article/pii/S2211124719314536 |