The potential of dendritic cell (DC)-based
immunotherapy to treat
cancer is, nowadays, well documented. Still, the clinical success of
immune checkpoint inhibitors has dampened the interest in anticancer DC vaccination. For highly life-threatening
tumors that are regarded as nonimmunogenic, such as
mesothelioma, however, T helper 1 immunity-biased DC-based
immunotherapy could still represent an attractive strategy. In this study, we took advantage of
photodynamic therapy (
PDT) to induce immunogenic cell death to generate
mesothelioma cell lysates for DC priming and evaluated such a
vaccine to treat peritoneal
mesothelioma. We found that the white light in vitro activation of the
photosensitizer OR141 led to
mesothelioma cell death, together with the release of bona fide danger signals that promote DC maturation. The administration of a
PDT-based DC
vaccine to mice bearing peritoneal
mesothelioma led to highly significant survival when compared with
sham or control animals treated with anti-CTLA4
antibodies. This was further supported by a strong CD8+ and CD4+ T cell response, characterized by an increased proliferation, cytotoxic activities and the expression of activation markers, including
interferon gamma (IFN). Moreover, the
PDT-based DC
vaccine led to a significant increase in IFN+ T cells infiltered within
mesothelioma, as determined by flow cytometry and immunohistochemistry. Finally, in vivo tracking of intraperitoneally administered DCs led us to document rapid chemotaxis towards
tumor-occupied lymphatics (vs.
lipopolysaccharide (LPS)-treated DC). DCs pulsed with
PDT-killed
mesothelioma cells also exhibited a significant increase in
CCR7 receptors, together with an intrinsic capacity to migrate towards the lymph nodes. Altogether, these results indicate that
PDT-based DC vaccination is particularly suited to induce a potent immune response against peritoneal
mesothelioma.