Photodynamic therapy (PDT) has long been known for capable of killing tumor cells and induces anti-tumor immunity. The mechanism of how PDT can enhance anti-tumor response is not clear. We tested the hypothesis that bone marrow derived dendritic cells (BMDCs) activated by PDT-generated tumor cell lysates (PDTTCL) can induce anti-tumor response in Lewis lung carcinoma (LLC), a poorly immunogenic tumor model. We found that LLC tumor growth was retarded by immunization with BMDCs pulsed by PDTTCL. Furthermore, therapeutic effects are observed in preexisting LLC tumor when PDT is combined with PDTTCL treated BMDCs and R848 (TLR7/8 ligand) therapy. This study aims to understand how PDT enhances tumor immunogenicity and provides insight to improve both in situ PDT and PDT vaccine efficacy in combating secondary disease. We found that stimulation of BMDCs with PDTTCL leads to dramatic increase in pro-inflammatory cytokine production, including IL-1β, which plays a critical role in PDT efficacy. Previous studies have shown that production and activation of IL-1β require both TLR signaling and activation of NLRP3 inflammasome. IL-1β production induced by PDTTCL in BMDCs is MyD88 dependent, but the activation of IL-1β appears to be dependent upon elastase and proteinase 3 rather than NLRP3 inflammasome. Together, our findings reveal a novel mechanism of IL-1β activation in BMDCs that does not require NLRP3 inflammasome in response to danger signals from tumor cell lysates.
- Copyright © 2013 by The American Association of Immunologists, Inc.