CpG oligodeoxynucleotide as immune adjuvant enhances photodynamic therapy response in murine metastatic breast cancer

Abstract

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.

Modern trends in biophotonics for clinical diagnosis and therapy to solve unmet clinical needs

“…A new approach combined immunostimulants with PDT to enhance anti‐tumor immunity. A study investigated PDT mediated by verteporfin and 690 nm light in combination with immunomodulation using CpG oligodeoxynucleotide . PDT with 5‐aminolevulinic acid (ALA) is known to be limited for applications in tumors of large volume mainly due to the limited penetration of topical photosensitization.…”

Breast cancer as photodynamic therapy target: Enhanced therapeutic efficiency by overview of tumor complexity

“…Peritumoral injection of CpG after PDT in mice gave improved local tumor control and a survival advantage compared to either treatment alone ( Figure 1). In conclusion, CpG may be a valuable dendritic cell-targeted immunoadjuvant to combine with PDT [46] . With regard to the TME, in addition to the cellular or biotic factors that modulate the photodynamic response, abiotic components also have a strong influence on PDT outcome.…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…2). 111 In addition to activating antitumor activity by DCs and T cells, various immune cells, including neutrophils, NK cells and macrophages, are stimulated after PDT and involved in tumor immunity. 107 Yu et al structured GO(HPPH)-PEG-HK nanoparticles loaded with PS HPPH and observed an effective antitumor effect not only on the primary tumor but also on the metastasis in the lung by activating DCs and CD8 + T lymphocytes.…”

“…For example, the presence of CpG oligodeoxynucleotides promotes the maturation and activation of DCs in vitro and in vivo, leading to tumor inhibition and a survival advantage. 111 In addition to activating antitumor activity by DCs and T cells, various immune cells, including neutrophils, NK cells and macrophages, are stimulated after PDT and involved in tumor immunity. 112,113 NK cells are among the most important immune cells in the body, given their participation in anti-infection, immune regulation and antitumor immunity.…”