Boosting Tumor-Specific Immunity Using PDT

Abstract

Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators. Activation of the innate immune response is necessary for subsequent induction of the adaptive arm of the immune system. This includes the priming of tumor-specific cytotoxic T lymphocytes (CTL) that have the capability to directly recognize and kill cells which display an altered self. The past decades have brought increasing appreciation for the importance of the generation of an adaptive immune response for long-term tumor control and induction of immune memory to combat recurrent disease. This has led to considerable effort to elucidate the immune effects PDT treatment elicits. In this review we deal with the progress which has been made during the past 20 years in uncovering the role of PDT in the induction of the tumor-specific immune response, with special emphasis on adaptive immunity.

The Course of Immune Stimulation by Photodynamic Therapy: Bridging Fundamentals of Photochemically Induced Immunogenic Cell Death to the Enrichment of T‐Cell Repertoire

“…Several landmark reviews by Castano et al (2006), Mroz et al (2011) and Meading et al . (2016) have described in depth how PDT is capable of eliciting tumor‐specific adaptive immunity . In this review, we will focus only on the major steps involved in achieving an adaptive antitumor response following photodynamic insult to tumors to bridge the fundamentals of photochemistry, ICD and adaptive immunity with the potential for enriching the T‐cell repertoire (Fig.…”

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…Ample evidence shows that both the innate and adaptive immune systems participate in PDT-induced tumour elimination (Nowis et al 2005;Castano et al, 2006). The immune response is activated by PDT-induced tumour cell death or damage, which triggers the release of various damage-associated molecular patterns (DAMPs) including heat shock protein 70 (HSP70), calreticulin (CRT), high-mobility group box 1 (HMDB1), and ATP (Korbelik 2006;Maeding et al 2016;Tanaka et al 2016). A particularly immunogenic type of cell death is necrosis, where a lot of DAMPs are released, but apoptotic and stressed cells contribute as well, especially if the extent of damage is large and/or rapidly peaks upon PDT application (Korbelik 2006).…”

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

“…103,104 Therefore, oxygen self-enriched nanoparticles are beneficial for not only the enhanced PDT effect but also for overcoming chemoresistance. 106 Kabingu et al demonstrated that local PDT can inhibit the growth of the primary tumor and the untreated distant tumors due to the infiltration of CD8 + T cells. Tumor cells undergoing apoptosis or necrosis release tumor-associated antigens.…”