title: Blocking TLR2 activity attenuates pulmonary metastases of tumor.
abstract: BACKGROUND
  Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis.
  
  
  RESULTS
  In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells. Multiple subtypes of TLRs were expressed on B16 cells and several human cancer cell lines; TLR2 mediated the invasive activity of these cells. High metastatic B16 cells released more heat shock protein 60 than poor metastatic B16-F1 cells. Importantly, heat shock protein 60 released by tumor cells caused a persistent activation of TLR2 and was critical in the constitutive activation of transcription factor Stat3, leading to the release of immunosuppressive cytokines and chemokines. Moreover, targeting TLR2 markedly reduced pulmonary metastases and increased the survival of B16-bearing mice by reversing B16 cells induced immunosuppressive microenvironment and restoring tumor-killing cells such as CD8(+) T cells and M1 macrophages. Combining an anti-TLR2 antibody and a cytotoxic agent, gemcitabine, provided a further improvement in the survival of tumor-bearing mice.
  
  
  CONCLUSIONS
  Our results demonstrate that TLR2 is an attractive target against metastasis and that targeting immunosuppressive microenvironment using anti-TLR2 antibody is a novel therapeutic strategy for combating a life-threatening metastasis.
authors: Molecular Immunology and Pharmacology Laboratory, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors: Hong-Zhen
authors: HZ
authors: Yang
authors: Bing
authors: B
authors: Cui
authors: Han-Zhi
authors: HZ
authors: Liu
authors: Su
authors: S
authors: Mi
authors: Jun
authors: J
authors: Yan
authors: Hui-Min
authors: HM
authors: Yan
authors: Fang
authors: F
authors: Hua
authors: Heng
authors: H
authors: Lin
authors: Wen-Feng
authors: WF
authors: Cai
authors: Wen-Jie
authors: WJ
authors: Xie
authors: Xiao-Xi
authors: XX
authors: Lv
authors: Xiao-Xing
authors: XX
authors: Wang
authors: Bing-Mu
authors: BM
authors: Xin
authors: Qi-Min
authors: QM
authors: Zhan
authors: Zhuo-Wei
authors: ZW
authors: Hu
mesh_terms: D000818:Animals; D018834:Chaperonin 60 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology
chemical_list: D018834:Chaperonin 60; D018925:Chemokines; D016207:Cytokines; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2