Abstract

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.

Highlights

  • Photodynamic therapy (PDT) is a cancer modality that combines three essential components of a photosensitizer (PS), harmless light, and molecular oxygen [1]

  • Clinical evidence is very scarce, numerous preclinical studies showed that PDT modality could potentially become a potent therapeutic option for cancer treatment

  • Researchers have explored several approaches aimed at overcoming the immunotolerance in treated tumors, attenuating the immunosuppressive tumorthe microenvironment (TME) and establishing a robust and systemic adaptive immune response that can obliterate distant tumor lesions

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Summary

Introduction

Photodynamic therapy (PDT) is a cancer modality that combines three essential components of a photosensitizer (PS), harmless light, and molecular oxygen [1]. It is based on the accumulation of a PS in pathological tissues, which can generate highly cytotoxic reactive oxygen species (ROS) upon its activation with a specific wavelength of light [2]. PDT presents unique advantages such as the selective uptake of PSs by tumor tissues, localized light exposure to the affected site, non-invasiveness feature, and simple procedure. As a result of this photodamage to the tumor and its microenvironment, a robust acute inflammatory response is produced at the tumor site [4,5].

Antitumor
Methods for 3D Tumor Generation
Hanging Drop Method
Liquid Overlay Method
Bioreactor-Based 3D Culture Method
Hydrogels
PDT and Innate Immune Response
PDT and Adaptive Immune Response
Experimental Studies on Immune Responses to PDT in Cancer Treatment
Clinical Studies on PDT Immune Responses in Cancer Treatment
Intracellular Accumulation of PSs
ER-Targeted PDT
Mitochondria Targeted PDT
Application of Nanotechnology
Experimental Models for Evaluation of PDT-Induced Antitumor Immune
Immunomodulation
Immunostimulants
Conclusions and Future Perspectives
Findings
Limitations
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