Photodynamic-immune checkpoint therapy eradicates local and distant tumors by CD8+ T cells
Menée à l'aide de deux modèles murins, cette étude montre que l'ablation d'une tumeur localisée par photothérapie dynamique favorise la réponse des lymphocytes T CD8+ et permet, en combinaison avec un inhibiteur de point de contrôle immunitaire, d'éradiquer une tumeur distante non traitée
Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces tumor burden and may induce T cell responses, providing a therapeutic option for mutated tumors. In this study, we applied PDT in two mouse tumor models and assessed its effect on outgrowth of PDT-treated and distant untreated tumors. PDT of established tumors resulted in complete tumor eradication in most mice, which were then protected against tumor re-challenge. Correspondingly, the therapeutic effect was abrogated upon systemic depletion of CD8+ T cells, indicating PDT-induced tumor antigen cross-presentation and T cell activation. In a double-tumor model, PDT of primary tumors induced enhanced infiltration of untreated distant tumors by CD8+ T cells, which significantly delayed their outgrowth. Combination therapy of PDT and CTLA-4 blocking antibodies significantly improved therapeutic efficacy and survival of double tumor-bearing mice. These results show that local tumor ablation by PDT induces CD8+ T cell responses crucial for systemic tumor eradication, which can be further enhanced by combination with immune checkpoint blockade. This combination of two clinically applied therapies may be a treatment strategy for advanced cancer without previous knowledge of tumor-specific antigens.