Lymphoma immunotherapy with CpG oligodeoxynucleotides requires TLR9 either in the host or in the tumor itself.
Established widely metastatic tumor was cured in a transplanted mouse B cell lymphoma model, by the combination of chemotherapy plus intratumoral injection of oligodeoxynucleotides containing unmethylated C-G motifs (CpG). This therapeutic effect required that the CpG be injected directly into the tumor and was dependent on CD8 T cells. Although the efficacy of CpG oligodeoxynucleotides has been thought to depend on the expression of TLR9, we unexpectedly found that tumor rejection did not require host expression of TLR9. By using a TLR9-deficient tumor and a TLR9KO host, we demonstrate that TLR9 expression either by the host or the tumor is required. These results indicate that activation of Ag presentation by cells within the tumor via TLR9 stimulation can be an effective form of immunotherapy. This study forms the basis of an ongoing clinical trial in patients with lymphoma.
Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305, USA.
Jiali
J
Li
Wenru
W
Song
Debra K
DK
Czerwinski
Bindu
B
Varghese
Satoshi
S
Uematsu
Shizuo
S
Akira
Arthur M
AM
Krieg
Ronald
R
Levy
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000276:immunology*
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9