Flagellin, the structural protein subunit of the bacterial flagellum, is specifically recognized by TLR-5 and has potent immunomodulatory effects. The antitumor effects of purified Salmonella typhimurium flagellin were evaluated in mice transplanted s.c. with a weakly immunogenic murine tumor or with its variant stably transfected to express the highly antigenic human HER-2 oncoprotein. Peritumoral administration of flagellin 8-10 days after tumor implantation did not affect the growth rate of the weakly immunogenic tumor but significantly inhibited growth of the antigenic variant tumor. In contrast, flagellin administered at the time of implantation of the antigenic tumor led to accelerated tumor growth. These contrasting effects of flagellin on tumor growth correlated with the type of immune response induced; i.e., late flagellin administration was assocd. with an increased IFN-g:IL-4 ratio and the decreased frequency of CD4+CD25+ T regulatory cells, whereas flagellin treatment at the time of tumor implantation decreased the IFN-g:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-contg. oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-contg. oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth.

Antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer / L. Sfondrini, A. Rossini, D. Besusso, A. Merlo, E. Tagliabue, S. Menard, A. Balsari. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 176:11(2006), pp. 6624-6630. [10.4049/jimmunol.176.11.6624]

Antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer

L. Sfondrini
Primo
;
A. Rossini
Secondo
;
D. Besusso;A. Balsari
Ultimo
2006

Abstract

Flagellin, the structural protein subunit of the bacterial flagellum, is specifically recognized by TLR-5 and has potent immunomodulatory effects. The antitumor effects of purified Salmonella typhimurium flagellin were evaluated in mice transplanted s.c. with a weakly immunogenic murine tumor or with its variant stably transfected to express the highly antigenic human HER-2 oncoprotein. Peritumoral administration of flagellin 8-10 days after tumor implantation did not affect the growth rate of the weakly immunogenic tumor but significantly inhibited growth of the antigenic variant tumor. In contrast, flagellin administered at the time of implantation of the antigenic tumor led to accelerated tumor growth. These contrasting effects of flagellin on tumor growth correlated with the type of immune response induced; i.e., late flagellin administration was assocd. with an increased IFN-g:IL-4 ratio and the decreased frequency of CD4+CD25+ T regulatory cells, whereas flagellin treatment at the time of tumor implantation decreased the IFN-g:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-contg. oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-contg. oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth.
CD4-positive T cell (CD25+; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Oligodeoxyribonucleotides Role: PAC (Pharmacological activity), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (CpG-contg.; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Receptors Role: BSU (Biological study, unclassified), BIOL (Biological study) (TLR-5 (Toll-like receptor-5) ; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Antitumor agents ; Cell proliferation ; Drug toxicity ; Neoplasm (antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Flagellins Role: ADV (Adverse effect, including toxicity), BSU (Biological study, unclassified), PAC (Pharmacological activity), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Interleukin 4 Role: BSU (Biological study, unclassified), BIOL (Biological study) (antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Mammary gland (carcinoma; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Carcinoma (mammary; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Cooperative phenomena (synergism; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer) ; Interferons Role: BSU (Biological study, unclassified), BIOL (Biological study) (g; antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer)
Settore MED/04 - Patologia Generale
2006
http://www.jimmunol.org/content/176/11/6624.abstract
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/25668
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