Antitumor Activity of the TLR-5 Ligand Flagellin in Mouse Models of Cancer

@article{citeulike:1530987, 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 associated with an increased IFN-{gamma}: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-{gamma}:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-containing oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-containing oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth.}, author = {Sfondrini, Lucia and Rossini, Anna and Besusso, Dario and Merlo, Andrea and Tagliabue, Elda and Menard, Sylvie and Balsari, Andrea }, citeulike-article-id = {1530987}, journal = {J Immunol}, keywords = {flagellin-tumor}, month = {June}, number = {11}, pages = {6624--6630}, posted-at = {2007-08-02 17:40:58}, priority = {2}, title = {Antitumor Activity of the TLR-5 Ligand Flagellin in Mouse Models of Cancer}, url = {http://www.jimmunol.org/cgi/content/abstract/176/11/6624}, volume = {176}, year = {2006} }

TY - JOUR ID - citeulike:1530987 L3 - citeulike-article-id:1530987 TI - Antitumor Activity of the TLR-5 Ligand Flagellin in Mouse Models of Cancer JF - J Immunol VL - 176 IS - 11 SP - 6624 EP - 6630 N2 - 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 associated with an increased IFN-{gamma}: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-{gamma}:IL-4 ratio and increased CD4+CD25+ T cell frequency. When the early flagellin treatment was combined with administration of CpG-containing oligodeoxynucleotides, tumor growth was completely suppressed, indicating synergy between flagellin and CpG-containing oligodeoxynucleotides. Together, these data provide evidence that flagellin can have contrasting effects on tumor growth. KW - flagellin-tumor AU - Sfondrini, Lucia AU - Rossini, Anna AU - Besusso, Dario AU - Merlo, Andrea AU - Tagliabue, Elda AU - Menard, Sylvie AU - Balsari, Andrea PY - 2006/06/01/ UR - http://www.jimmunol.org/cgi/content/abstract/176/11/6624 ER -