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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 [Int J Oncol] 2008 Feb; Vol. 32 (2), pp. 499-507. - Publication Year :
- 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 :
- Animals
CD4-Positive T-Lymphocytes metabolism
Cancer Vaccines
Disease Models, Animal
Immune System metabolism
Interleukin-12 metabolism
Interleukin-2 Receptor alpha Subunit biosynthesis
Kinetics
Lymph Nodes pathology
Mice
Neoplasms metabolism
Cytokines metabolism
Gene Expression Regulation, Neoplastic
Human papillomavirus 16 metabolism
Immune System immunology
Immunotherapy methods
Interleukin-12 chemistry
Neoplasms virology
Subjects
Details
- Language :
- English
- ISSN :
- 1019-6439
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 18202774