CpG oligodeoxynucleotide as immune adjuvant enhances photodynamic therapy response in murine metastatic breast cancer.
Breast cancer is the most common cause of cancer death in women. The side effects and complications following current breast cancer therapy can be devastating. Moreover, the prognosis in late stages of the diseases is usually poor. Photodynamic therapy (PDT) is a promising cancer treatment modality that is capable of both local tumor destruction and immune stimulation. However, treatment with PDT alone is often non-curative due to tumor-induced immune cell dysfunction and immune suppression. This phenomenon has motivated a new approach by combining immunostimulants with PDT to enhance anti-tumor immunity. In the present study, we investigated PDT mediated by verteporfin and 690 nm light delivered 15 min later, in combination with an immunomodulation approach using CpG oligodeoxynucleotide for the treatment of 4T1 metastatic breast cancer in a BALB/c immunocompetent mouse model. In vitro, CpG primed immature dendritic cells (DC) via toll like receptor 9 to phagocytose PDT killed tumor cells leading to DC maturation and activation. Peritumoral injection of CpG after PDT in mice gave improved local tumor control and a survival advantage compared to either treatment alone (p < 0.05). CpG may be a valuable dendritic cell targeted immunoadjuvant to combine with PDT.
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Dermatology, Harvard Medical School, Boston, MA, USA.
Yumin
Y
Xia
Gaurav K
GK
Gupta
Ana P
AP
Castano
Pawel
P
Mroz
Pinar
P
Avci
Michael R
MR
Hamblin
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D018899:CpG Islands; D003713:Dendritic Cells / Q000166:cytology; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D010587:Phagocytosis; D010641:Phenotype; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000166:cytology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D017319:Photosensitizing Agents
CpG oligodeoxynucleotide; breast cancer; dendritic cells; photodynamic therapy