39 - Freie Mitteilung
Clinical works I
16. Mai 2019, 08:30 - 10:00, Bellavista 2, 6. OG
Low dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of malignant pleural mesothelioma
S. Cavin, J. Faget, A. Gkasti, Y. Hao, E. Meylan, J. Y. Perentes, Presenter: S. Cavin (Lausanne)
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with limited treatment options. An increased 5-year survival rate was reported in patients with MPM managed by multimodal therapy including extended pleural decortication and photodynamic therapy (PDT). Recent data has suggested that durable disease control in MPM patients was associated to patient immunization against their cancer. Here we determined the immunological impact of low dose Visudyne (BPD-MA)-mediated PDT (L-PDT) in a syngeneic immunocompetent murine model of MPM.
MPM AE17 cells were implanted in C57BL/6 mice (n=24) and grown up to 30mm3 in volume. Animals were then separated into two treatment groups: L-PDT (BPD-MA 0.4 mg/kg i.v., 10J/cm2, 50 mW/cm2, drug-light interval 10 min, n=12) and control (BPD-MA 0.4 mg/kg i.v., no light exposure, n=12). Half of each treatment group was sacrificed at day 2 while the other half at day 7. Tumors were harvested and processed for analysis by 16-color flow cytometry to extract the tumor immune signature and determine its response to treatment.
We observed no difference in tumor size in this study between treatment groups. Multi-color flow cytometry analysis revealed a significant increase in the proportion of CD8+ T cells (CD8+CD3+, p<0.05) as well as an enhanced activation of macrophages (p<0.05), CD11b+ dendritic cells (p<0.05) and of myeloid derived suppressor cells (mMDSCs, p<0.05) two days after L-PDT compared to controls. Interestingly, seven days after L-PDT, while CD8+ T cells remained high (p<0.05), the proportion of macrophages and of CD4+CD103+ cells went down (p<0.05). In parallel, the activation status of CD11b+ dendritic cells and mMDSC were decreased (p<0.05) while the activation status of macrophages was increased (p<0.05).
L-PDT created a marked modification of the immune signature of MPM that seem to favor a CD8+ cytotoxic T cell response. Further work combining this approach with immune checkpoint inhibition may help boost the impact of immunotherapy, particularly in tumors with low immunogenicity such as MPM.