Preclinical and Clinical Evidence of Immune Responses Triggered in Oncologic Photodynamic Therapy: Clinical Recommendations

Abstract

Photodynamic therapy (PDT) is an anticancer strategy utilizing light-mediated activation of a photosensitizer (PS) which has accumulated in tumor and/or surrounding vasculature. Upon activation, the PS mediates tumor destruction through the generation of reactive oxygen species and tumor-associated vasculature damage, generally resulting in high tumor cure rates. In addition, a PDT-induced immune response against the tumor has been documented in several studies. However, some contradictory results have been reported as well. With the aim of improving the understanding and awareness of the immunological events triggered by PDT, this review focuses on the immunological effects post-PDT, described in preclinical and clinical studies. The reviewed preclinical evidence indicates that PDT is able to elicit a local inflammatory response in the treated site, which can develop into systemic antitumor immunity, providing long-term tumor growth control. Nevertheless, this aspect of PDT has barely been explored in clinical studies. It is clear that further understanding of these events can impact the design of more potent PDT treatments. Based on the available preclinical knowledge, recommendations are given to guide future clinical research to gain valuable information on the immune response induced by PDT. Such insights directly obtained from cancer patients can only improve the success of PDT treatment, either alone or in combination with immunomodulatory approaches.

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences

“…As a photosensitizer, PpIX mediates energy transfer from light photons to oxygen molecules to generate reactive oxygen species that lead to oxidation and destruction of membranes, proteins and other vital intracellular structures [ 46 , 47 ]. Some of the cell death mechanisms initiated in this manner effectively stimulate the immune response, adding an intriguing systemic effect to this otherwise local treatment modality [ 48 , 49 ].…”

Nanobody-targeted photodynamic therapy induces significant tumor regression of trastuzumab-resistant HER2-positive breast cancer, after a single treatment session

“…To explore more about the direct effect of PDT on the vasculature, intravital microscopy imaging could be used to provide longitudinal information on the kinetics and localization of the anti-HER2 nanobody-PS in detail [ 52 ]. To investigate complete tumor remission, a longer follow-up of 90 days would be necessary, and, it could also be interesting to investigate our model in immunocompetent mice, as PDT has a strong immune component and the requirement of the immune system for avoiding relapse from cancer is becoming evident [ 64 – 67 ]. Nevertheless, for a more clinically relevant context, nanobody-targeted PDT could be investigated in the postsurgical setting, for HER2-positive breast cancer in primary tumors, which did not respond to neoadjuvant therapy and/or became resistant to trastuzumab, compared to standard clinical treament.…”

The Potential of Nanobody-Targeted Photodynamic Therapy to Trigger Immune Responses

“…Both NB-PDT and its conventional counterpart initially cause extensive damage to the primary tumor and to the tumor vasculature [2,15]. In addition, the conventional approach has been described to also stimulate an antitumor immunity [3,4]. Consequently, this local treatment can induce a systemic effect, a feature that is highly desirable for protection against metastasis and recurrences.…”

“…Upon PS activation, reactive oxygen species are generated that ultimately lead to cell death [1,2]. Besides direct cytotoxicity, damage to the tumor vasculature and the potential to stimulate an antitumor immune response have been reported [2][3][4]. This last aspect is of particular interest since a local treatment such as PDT, making use of locally applied light at the tumor site, could develop systemic effects via the activation of the immune system.…”