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Doxorubicin pretreatment enhances FAPα/survivin co-targeting DNA vaccine anti-tumor activity primarily through decreasing peripheral MDSCs in the 4T1 murine breast cancer model
- Source :
- Oncoimmunology, OncoImmunology, Vol 9, Iss 1 (2020)
- Publication Year :
- 2020
- Publisher :
- Taylor & Francis, 2020.
-
Abstract
- The tumor microenvironment (TME) provides necessary nutrition for tumor growth and recruits immunosuppressive factors including regulatory T cells and myeloid-derived suppressor cells (MDSCs) to inhibit the anti-tumor immune response induced by immunotherapy. As a main TME component, cancer associated fibroblasts (CAFs) can restrain T cell infiltration and activity through extracellular matrix remodeling. Vaccines targeting fibroblast-activating protein α (FAPα), which is mainly expressed on the CAF surface, can eliminate CAFs in tumors and regulate the TME, enhancing the potency of T cell-mediated anti-tumor effects. However, the anti-tumor effects were not fully realized as the tumor induces a large number of peripheral MDSCs during its growth, rendering the body of mice in an immunosuppressive state and preventing the vaccine from inducing effective anti-tumor immune responses. Here, we developed a dual-targeted DNA vaccine OsFS, targeting tumor matrix antigen FAPα and tumor cell antigen survivin simultaneously, exhibited enhanced antineoplastic effects in an established breast cancer model. Moreover, doxorubicin (Dox) pretreatment to remove the peripheral MDSCs induced to regulate the peripheral immune environment could further facilitate the anti-tumor activity of the vaccine. These results indicated that combination treatment of the tumor cells and the TME dual-targeting vaccine plus Dox could effectively realize the anti-tumor activity of the vaccine by decreasing immunosuppressive factors and inducing more tumor-infiltrating lymphocytes, which may offer important guidance for clinical research regarding the combination of the DNA vaccine with low-dose Dox.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
fibroblast activating protein α
Survivin
Immunology
Breast Neoplasms
doxorubicin
Cancer Vaccines
DNA vaccination
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
Antigen
Cell Line, Tumor
Endopeptidases
Vaccines, DNA
Immunology and Allergy
Medicine
Animals
Doxorubicin
RC254-282
Original Research
Tumor microenvironment
business.industry
Myeloid-Derived Suppressor Cells
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Membrane Proteins
Immunotherapy
RC581-607
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Myeloid-derived Suppressor Cell
Cancer research
Immunologic diseases. Allergy
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 2162402X and 21624011
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Oncoimmunology
- Accession number :
- edsair.doi.dedup.....8777f3511124d51a38fed649c4300e30