Current Prospects for Treatment of Solid Tumors via Photodynamic, Photothermal, or Ionizing Radiation Therapies Combined with Immune Checkpoint Inhibition (A Review)

Abstract

Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy to destroy cancer tissue. Ionizing radiation therapy (RT) and photothermal therapy (PTT) are two other treatment modalities that employ photons (with wavelengths either shorter or longer than PDT, respectively) and also cause tissue damage and immunomodulation. Research on the three modalities has occurred in different “silos”, with minimal interaction between the three topics. This is happening at a time when immune checkpoint inhibition (ICI), another focus of intense research and clinical development, has opened exciting possibilities for combining PDT, PTT, or RT with ICI to achieve improved therapeutic benefits. In this review, we surveyed the literature for studies that describe changes in anti-tumor immunity following the administration of PDT, PTT, and RT, including efforts to combine each modality with ICI. This information, collected all in one place, may make it easier to recognize similarities and differences and help to identify new mechanistic hypotheses toward the goal of achieving optimized combinations and tumor cures.

Nanoparticle-Mediated Delivery Systems in Photodynamic Therapy of Colorectal Cancer

“…PDT is also capable of triggering an inflammatory response, which causes the infiltration of leukocytes to the target area and the release of pro-inflammatory factors and cytokines [37]. Moreover, ROS can further elicit immunogenic cell death, which is accompanied by the release of damage-associated molecular patterns (DAMPs) from the the damaged/dying cells, which then act as danger signals [37,38]. Upon the recognition of DAMPs, the innate immune phagocytes (macrophages, neutrophils and dendritic cells) can neutralize and remove cellular debris [37].…”

Photodynamic Therapy for Pancreatic Ductal Adenocarcinoma

“…Immune checkpoint blockade (ICB) therapy has demonstrated promising responses in several types of cancers. A recent study has surveyed the effect of PDT, RT, and PTT on stimulating a number of immune modulatory effects [124]. In pancreatic cancer, however, ICB therapy has shown limited benefits, since its TME has been shown to be highly immunosuppressive [125].…”

Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer

“…Several studies on the combined effect of PDT with photosensitizers and immune checkpoint inhibition in preclinical models aiming to improve the therapeutic efficiency have been reported [21]. Enhanced anti-tumor efficacy was demonstrated in murine tumor models including breast, subcutaneous, melanoma, renal cell carcinoma, and colon through a combined action of checkpoint inhibitors and PDT.…”

“…The local treatment of tumor together with the systemic administration of checkpoint inhibitors primed an immune response resulting in increased infiltration of activated CD8+ T cells in the primary tumor, but also in secondary tumors/metastases indicating an abscopal effect. Moreover, an immunological memory effect was developed as PDT-treated tumor-free mice were protected against developing new tumors when re-challenged [21][22][23][24][25].…”