Evaluation of a new therapeutic strategy in Nasopharyngeal carcinoma: Photodynamic Therapy using 5-aminolevulinic acid

Nasopharyngeal carcinoma (NPC) is a chemo-radiosensitive cancer leading to an effective control of the primary tumor with a 10-year disease-free survival rate of 67-71%. However, due to late diagnosis and extensive metastatic formation, the survival rate decreases drastically to 29-54%. Thus, for recurrent or persistent local tumors, there are few treatment options left. Photodynamic Therapy (PDT) could be a relevant candidate by inducing direct cell death and the activation of a systemic immune response. Indeed, NPC is characterized by an immunosuppressive environment dominated by regulatory T lymphocytes and tumor-derived exosomes (NPC-Exo). We demonstrated that NPC-Exo induce dendritic cells with tolerogenic properties favouring the suppressive microenvironment [1]. Moreover, the team's work has established the ability of PDT to induce the release of ovarian tumor derived extracellular vesicles capable of activating immune cells [2]. In this context, the objective of this study is to evaluate, on one hand, the effectiveness of a new therapeutic strategy in the NPC namely a photodynamic therapy using 5-aminolevulinc acid (5-ALA) and on the other hand to assess the impact of PDT on the deleterious function of NPC-Exo. Two NPC cell lines, C17 and C666-1 were used. First, we evaluate the capacity of the cell to metabolize the photosensitizer PpIX. And then, we validated the effectiveness of PDT using an ATP-based viability assay. After the determination of the optimal lighting protocol, we will assess the ability of the PDT strategy to modulate the secretome (ELISA) and NPC-Exo phenotype and properties (Suppressive test). This strategy will be confirmed in vivo in a humanized mouse model of NPC. We have shown that C17 and C666-1 cell lines are able to incorporate 5-ALA and to metabolize the photosensitizer PpIX in a dose and time dependent manner. C17 cells appear receptive to PDT treatment with significant cell death. We expected that photodynamic therapy strategy could allow a modification in cytokines production, NPC-Exo fonction and could induce tumor regression in mouse model. Taken together, these results seem to indicate that 5-ALA-mediated PDT could be a promising treatment of NPCs as an adjuvant therapy to conventional anti-cancer therapies.