Tumor cells prevent mouse dendritic cell maturation induced by TLR ligands.
Tumor cells can evade the immune system through several mechanisms, one of which is to block DC maturation. It has been suggested that signaling via Toll-like receptors (TLR) may be involved in the induction of prophylactic anti-cancer immunity and in the treatment of established tumors. In the present study we found that high numbers of tumor cells interfere with BMDC activation induced by the TLR ligands LPS and poly IC. Tumor cells blocked TLR3- and TLR4-mediated induction of MHCII and the co-stimulatory molecules CD40 and CD86, as well as the cytokines IL-12, TNF-alpha and IL-6. Importantly, tumor cells induced inhibitory molecules (B7-DC, B7-H1 and CD80) on spleen DC in vivo and on BMDC, even in the presence of TLR ligands. Moreover, after a long exposure with tumor cells, purified BMDC were unable to respond to a second challenge with TLR ligands. The failure of tumor exposed-BMDC to express co-stimulatory molecules and cytokines in the presence of TLR ligands has implications for the future development of DC-based cancer immune therapies using TLR ligands as adjuvants for the activation of DC.
Idoyaga
Juliana
J
Research Unit on Autoimmune Diseases, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Apartado Postal A-047, Coahuila No. 5, Col. Roma, Código Postal 06703, México DF, México.
Moreno
José
J
Bonifaz
Laura
L
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics; D060890:B7-H1 Antigen; D001854:Bone Marrow Cells / Q000166:cytology; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D034801:Mastocytoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D011070:Poly I-C / Q000494:pharmacology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D013154:Spleen / Q000166:cytology; D051196:Toll-Like Receptor 3 / Q000187:drug effects* / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D019013:CD40 Antigens; C498919:Cd274 protein, mouse; C497965:Cd86 protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D011070:Poly I-C