Photodynamic therapy: illuminating the road from cell death towards anti-tumour immunity

Abstract

Photodynamic therapy (PDT) utilizes the destructive power of reactive oxygen species generated via visible light irradiation of a photosensitive dye accumulated in the cancerous tissue/cells, to bring about their obliteration. PDT activates multiple signalling pathways in cancer cells, which could give rise to all three cell death modalities (at least in vitro). Simultaneously, PDT is capable of eliciting various effects in the tumour microenvironment thereby affecting the tumour-associated/-infiltrating immune cells and by extension, leading to infiltration of various immune cells (e.g. neutrophils) into the treated site. PDT is also associated to the activation of different immune phenomena, e.g. acute-phase response, complement cascade and production of cytokines/chemokines. It has also come to light that, PDT is capable of activating 'anti-tumour adaptive immunity' in both pre-clinical as well as clinical settings. Although the ability of PDT to induce 'anti-cancer vaccine effect' is still debatable, yet it has been shown to be capable of inducing exposure/release of certain damage-associated molecular patterns (DAMPs) like HSP70. Therefore, it seems that PDT is unique among other approved therapeutic procedures in generating a microenvironment suitable for development of systemic anti-tumour immunity. Apart from this, recent times have seen the emergence of certain promising modalities based on PDT like-photoimmunotherapy and PDT-based cancer vaccines. This review mainly discusses the effects exerted by PDT on cancer cells, immune cells as well as tumour microenvironment in terms of anti-tumour immunity. The ability of PDT to expose/release DAMPs and the future perspectives of this paradigm have also been discussed.

Danger signalling during cancer cell death: origins, plasticity and regulation

“…28 Could the induction of a viral response-like gene expression (VRGE) programme be a general requisite of ICD? Some preliminary evidence 29 or retrospective analysis 30 indeed suggest that certain known ICD inducers, like doxorubicin and Hyp-PDT (Table 1), might instigate in the cancer cells a gene signature that resembles the VRGE programme 29,30 ( Figure 2). The protein products of various VRGE-related genes upregulated by doxorubicin (Figure 2a) or Hyp-PDT (Figure 2b) form an intricate evidence-based network; which is possibly a part of the host cell's viral response-like reaction during ICD.…”

“…29 (b) This is an evidence-based network of the proteins whose genes showed an upregulated expression in the T24 human bladder cancer cells retrieved 8 h after hypericin-based photodynamic therapy (Hyp-PDT). 30 The types of evidence behind the network and the corresponding color code scheme are mentioned in the inset. The genes were considered to have role in a viral response based on data available in the GeneCards database version 3.09 (http:// www.genecards.org/), wherever applicable.…”

ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death

“…2,[16][17][18] In immunological terms ICD is characterized by increased maturation or stimulation of DCs accompanied by IL1B production, which is required for the subsequent stimulation and proliferation of antitumorigenic, IFNG-producing, CD4 + or CD8 + T cells; 11,13 all of which together are indispensible for ICD's ability to induce potent antitumor immunity. 2,19 We recently characterized that hypericin-based photodynamic therapy [19][20][21] causes induction of bona fide immunogenic cancer cell death. 9,10,17 Hypericin is an endoplasmic reticulum-associated photosensitiser, 14 which when activated by light, evokes the production of reactive oxygen species, photooxidative (phox) stress-mediated loss-of-function of ATP2A2 (ATPase, Ca++ transporting, cardiac muscle, slow twitch 2, also called sarcoplasmic/endoplasmic reticulum calcium ATPase 2), disruption of ER-Ca 2+ homeostasis and induction of phox-ER stress.…”

Anti-tumor immunity of BAM-SiPc-mediated vascular photodynamic therapy in a BALB/c mouse model

“…The primary target of such a treatment protocol is presumably the tumor cells. 11 In contrast, vascular PDT (VPDT) aims to disrupt the tumorinnervating vasculature by activating the PS while it is present in the vessel lumen. The PS could be targeted to the vessels by conjugation with specific peptides.…”