title: CC chemokine ligand 21 enhances the immunogenicity of the breast cancer cell line MCF-7 upon assistance of TLR2.
abstract: CC chemokine ligand 21 (CCL21) is a known attractant for CCR7-positive (CCR7+) cells, but its additional role in the immunogenicity of CCR7+ cells remains poorly understood. This study explored the effects of CCL21-CCR7 ligation on cancer immunogenicity and related antitumor immune response, in the presence and absence of mitomycin C (MMC) treatment. CCL21-CCR7 binding upregulated human leukocyte antigen class I-restricted tumor antigen presentation with increased expression of human leukocyte antigen class I and transporter associated with antigen processing-1. In addition, CCL21 restrained the tumor-derived immunosuppressive factors FasL and transforming growth factor-β. Consequently, CCL21 facilitated cancer-educated lymphocytes reaction in vitro. In the tumor-bearing mouse, CCL21 inhibited tumor growth and prolonged mouse survival via lymphocytes, especially in CCR7+ cancer cells. Furthermore, Toll-like receptor 2 activation of lymphocytes assisted the tumor-suppression functions of CCL21, in vitro and in vivo. This study implies that CCL21 improved the immunogenicity of the CCR7+ breast cancer cell line even with MMC treatment and triggered antitumor response by lymphocytes. These findings provide a new insight into the research and application of CCL21-associated antitumor response.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangdong Province 510515, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Lu
authors.forename: Z L
authors.initials: ZL
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Lei
authors.forename: P
authors.initials: P
authors.lastname: Hu
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Xing
authors.forename: X T
authors.initials: XT
authors.lastname: Jiang
authors.forename: H J
authors.initials: HJ
authors.lastname: Liu
authors.forename: Z G
authors.initials: ZG
authors.lastname: Zhu
authors.forename: W H
authors.initials: WH
authors.lastname: Li
authors.forename: H F
authors.initials: HF
authors.lastname: Zhu
authors.forename: N
authors.initials: N
authors.lastname: Fu
authors.forename: G X
authors.initials: GX
authors.lastname: Shen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017951:Antigen Presentation; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D054421:Chemokine CCL21 / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D054400:Receptors, CCR7 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D054421:Chemokine CCL21; D053222:Fas Ligand Protein; D008024:Ligands; D012333:RNA, Messenger; D054400:Receptors, CCR7; D051195:Toll-Like Receptor 2; D053773:Transforming Growth Factor beta1; D016685:Mitomycin