Changes in expression of genes involved in antitumor immunity in mice vaccinated with tumor vaccine composed of irradiated syngeneic tumor cells and CpG oligodeoxynucleotides.
In our previous studies, it has been demonstrated that in more than 80% of mice long-lasting antitumor immunity has been established following intraperitoneal (i.p.) vaccination with tumor vaccine composed of irradiated syngeneic tumor cells and CpG ODNs class C. The aim of this study was, therefore, to investigate molecular mechanisms through which this vaccine triggers the immunity and to define genes particularly involved in this process. Changes in gene expression were followed in mononuclear cells isolated from peritoneal lavages, spleens and bone marrow samples. The expression of 84 genes significant for T-cell and B-cell activation as well as genes engaged in activation of macrophages, NK cells and DCs was determined using the RT2- Profiler PCR array. It has been observed that this tumor vaccine induces the up-regulation of genes involved in activation, proliferation and survival of memory T-cells (Cd8a, Cd8b1, Prlr, Was, Cxcl12, Il12, Sftpd, Tnfrsf13c, Il15, Il18), and prevents the activation of genes involved in generation of Treg and induction of immune tolerance (Sit1, Sla2, Cd1d1, Pdcd1lg2, Pawr, Socs5, Il27, Il4). We may conclude based on results of gene expression analysis, that tumor vaccine fine-tunes the proportion of cytotoxic to regulatory lymphocytes having an important impact on the induction and maintenance of memory cells in bone marrow.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
Petra
P
Cerkovnik
Division of Medical Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
Barbara Jezeršek
BJ
Novaković
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
Vida
V
Stegel
Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. Electronic address: snovakovic@onko-i.si.
Srdjan
S
Novaković
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D059467:Transcriptome / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation
C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D009838:Oligodeoxyribonucleotides
CpG ODNs; Gene expression; Tumor vaccine; Whole tumor cells