Back to Search
Start Over
Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-19 (2018), Nature Communications
- Publication Year :
- 2018
- Publisher :
- Nature Publishing Group, 2018.
-
Abstract
- Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by stimulating CD8+ T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors. We found localized breast and pancreatic cancers induce systemic decreases in cDC1s and their progenitors. Mechanistically, tumor-produced granulocyte-stimulating factor downregulates interferon regulatory factor-8 in cDC progenitors, and thus results in reduced cDC1 development. Tumor-induced reductions in cDC1 development impair anti-tumor CD8+ T-cell responses and correlate with poor patient outcomes. These data suggest immune surveillance can be impaired by tumor-induced alterations in cDC development.<br />Tumors escape the immune system through many mechanisms. Here the authors show that certain tumors inhibit anti-tumor immunity by stopping the production of conventional dendritic cells (cDCs) in the bone marrow, therefore depleting the pool of cDCs available to present antigen to CD8+ T cells.
- Subjects :
- 0301 basic medicine
T-Lymphocytes
Thrombomodulin
medicine.medical_treatment
Cellular differentiation
General Physics and Astronomy
CD8-Positive T-Lymphocytes
Mice
0302 clinical medicine
lcsh:Science
Immunologic Surveillance
Oligonucleotide Array Sequence Analysis
Mice, Inbred BALB C
Multidisciplinary
Stem Cells
Cell Differentiation
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Antigens, Surface
Interferon Regulatory Factors
Cytokines
Female
Immunotherapy
Myelopoiesis
Integrin alpha Chains
Science
Antineoplastic Agents
Bone Marrow Cells
Breast Neoplasms
Article
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Antigens, CD
Immunity
medicine
Animals
Humans
business.industry
Dendritic Cells
General Chemistry
Dendritic cell
Mice, Inbred C57BL
Pancreatic Neoplasms
Disease Models, Animal
030104 developmental biology
Tumor progression
Cancer research
lcsh:Q
Bone marrow
IRF8
business
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....8d98f15d7110290a246baf02cefa5b57