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IL-12 immunotherapy of minimal residual disease in murine models of HPV16-associated tumours: induction of immune responses, cytokine production and kinetics of immune cell subsets
- Source :
- International Journal of Oncology.
- Publication Year :
- 2008
- Publisher :
- Spandidos Publications, 2008.
-
Abstract
- We have established animal models of HPV16-associated tumours with distinct levels of MHC class I expression. This model was used for examination of immune responses, production of cytokines and kinetics of immune cell subsets after IL-12 therapy of minimal residual tumour disease induced by CBA-4A (cyclophosphamide derivative) treatment. Upregulation of cytokine production was detected, compared to control animals without tumours. No differences in Th1/Th2 polarization of the immune responses after immunotherapy in animals bearing tumours with different surface expression of MHC class I molecules were observed. In the spleens of TC-1 (MHC class I+) but not of TC-1/A9 (MHC class I-) treated tumour-bearing animals, the cytotoxic CD8+ cells detectable in 51Cr microcytotoxicity assay, were found. In the spleens of TC-1/A9 but not of TC-1 tumour-treated animals, the NK activity measured as the lysis of NK-sensitive YAC-1 targets was detected. Down-regulation of the CD4+ and CD8+ subpopulations in spleens of tumour-bearing animals were not restored after therapy. The percentage of CD25+/CD4+ T regulatory (Treg) cells in lymph nodes remained unchanged. The cytoreductive chemotherapy led to strong upregulation and accumulation of immunosuppressive immature myeloid Gr-1+/CD11b+ cells (IMC) in the spleens of treated animals. The accumulation of Gr-1+/CD11b+ cells was significantly decreased after subsequent IL-12 immunotherapy. These data suggest that elimination of IMC after IL-12 immunotherapy may be responsible for the improvement of antitumour responses after adjuvant IL-12 vaccination for the treatment of CMRTD.
- Subjects :
- CD4-Positive T-Lymphocytes
Cancer Research
medicine.medical_treatment
Cancer Vaccines
Natural killer cell
Mice
Immune system
Neoplasms
MHC class I
medicine
Animals
Cytotoxic T cell
IL-2 receptor
Human papillomavirus 16
biology
Interleukin-2 Receptor alpha Subunit
Immunotherapy
Interleukin-12
Gene Expression Regulation, Neoplastic
Disease Models, Animal
Kinetics
medicine.anatomical_structure
Cytokine
Oncology
Immune System
Immunology
biology.protein
Cytokines
Lymph Nodes
CD8
Subjects
Details
- ISSN :
- 17912423 and 10196439
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology
- Accession number :
- edsair.doi.dedup.....552b55a26affb3186a439cd6e8c443b2