The intratumoral application of poly-G-oligodeoxynucleotides does not augment the naturally induced antitumoral CD8-T-cell response in P815 mastocytomas.
DNA sequences containing CpG have been described to induce a strong immune reaction by acting on a variety of immune cells including a strong and pronounced antitumoral response. Poly-G-oligodeoxynucleotides (ODNs) on the other hand have been attributed the preferential induction of CD8-T-cell proliferation when used in vitro. This activity led us to the investigation of the possible antitumoral properties of poly-G-ODNs in an established CD8-dependent tumor eradication model. We used the well described poly-G-ODN 1628 in its capacity to enhance antitumoral CD8 response in the cutaneous mastocytoma P815. When injecting 30 microg of the purified phosphothioate-modified oligo into the tumor bearing area of P815 challenged mice for up to 12 consecutive days we did not observe increased tumor rejection as compared to the group of mice injected with a control oligo. The 1628-injected mice did not produce higher numbers of P815-specific CD8 cells as measured by P1A-, and P1E-tetramer staining and Immunoscope analysis. Furthermore, tumor-specific CD8 cells in 1628 did not show enhanced antitumoral cytotoxicity when analyzing lymphocyte-tumor cell co-cultures or transcription of the cytotoxic CD8-cell associated molecules interferon gamma, FAS ligand, perforin, or granzyme B by quantitative real-time RT-PCR. These experiments show that there is no enhanced induction of an antitumoral CD8 response after in situ administration of poly-G-ODNs in the P815 mastocytoma model.
Mempel
Martin
M
Department of Immunology, Institut Pasteur, Unité de Biologie Moléculaire du Gène, INSERM U277, 25 rue du Dr. Roux, 75015 Paris, France. m.mempel@lrz.tum.de
Ronet
Catherine
C
Lemaitre
Fabrice
F
Lim
Annick
A
Kourilsky
Philippe
P
Gachelin
Gabriel
G
Musette
Philippe
P
D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D053804:Granzymes; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D034801:Mastocytoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D054353:Perforin; D011068:Poly G / Q000494:pharmacology*; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism; D013873:Thionucleotides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D052899:Pore Forming Cytotoxic Proteins; D013873:Thionucleotides; D054353:Perforin; D011068:Poly G; D007371:Interferon-gamma; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases