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Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment.
- Source :
-
Cell reports [Cell Rep] 2019 Oct 08; Vol. 29 (2), pp. 406-421.e5. - Publication Year :
- 2019
-
Abstract
- Over 80% of pancreatic ductal adenocarcinoma (PDA) patients are diagnosed with non-resectable late-stage disease that lacks effective neoadjuvant therapies. Stereotactic body radiation therapy (SBRT) has shown promise as an emerging neoadjuvant approach for treating PDA, and here, we report that its combination with local interleukin-12 (IL-12) microsphere (MS) immunotherapy results in marked tumor reduction and cures in multiple preclinical mouse models of PDA. Our findings demonstrate an increase of intratumoral interferon gamma (IFNγ) production following SBRT/IL-12 MS administration that initiates suppressor cell reprogramming and a subsequent increase in CD8 T cell activation. Furthermore, SBRT/IL-12 MS therapy results in the generation of systemic tumor immunity that is capable of eliminating established liver metastases, providing a rationale for follow-up studies in advanced metastatic disease.<br /> (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
CD8-Positive T-Lymphocytes immunology
Cell Line, Tumor
Cellular Reprogramming
Humans
Immunity
Interferon-gamma metabolism
Lymphocyte Activation immunology
Mice, Inbred C57BL
Microspheres
Models, Biological
Myeloid Cells pathology
Survival Analysis
Tumor Burden
Interleukin-12 therapeutic use
Pancreatic Neoplasms immunology
Pancreatic Neoplasms therapy
Radiosurgery
Tumor Microenvironment immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 29
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 31597100
- Full Text :
- https://doi.org/10.1016/j.celrep.2019.08.095