Photodynamic therapy-mediated immune responses in three-dimensional tumor models

Photodynamic therapy (PDT) is a promising non-invasive phototherapeutic approach for cancer therapy that can eliminate local tumor cells and produce systemic antitumor immune responses. In recent years, significant efforts have been made in developing strategies to further investigate the immune mechanisms triggered by PDT. The majority of in vitro experimental models still rely on the two-dimensional (2D) cell cultures that do not mimic a three-dimensional (3D) cellular environment in the human body, such as cellular heterogeneity, nutrient gradient, growth mechanisms, and the interaction between cells as well as the extracellular matrix (ECM) and therapeutic resistance to anticancer treatments. In addition, in vivo animal studies are highly expensive and time consuming, which may also show physiological discrepancies between animals and humans. In this sense, there is growing interest in the utilization of 3D tumor models, since they precisely mimic different features of solid tumors. This review summarizes the characteristics and techniques for 3D tumor model generation. Furthermore, we provide an overview of innate and adaptive immune responses induced by PDT in several in vitro and in vivo tumor models. Future perspectives are highlighted for further enhancing PDT immune responses as well as ideal experimental models for antitumor immune response studies.