Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy

Zheng, Yang; Yin, Guifang; Le, Vanminh; Zhang, Anle; Chen, Siyu; Liang, Xin; Liu, Jianwen

doi:10.7150/ijbs.12852

Cited by 81 publications

(65 citation statements)

References 35 publications

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“…This exposure of immunogenic molecules after NB-PDT was the next event explored in this study. Conventional PDT is described to induce exposure of HSP70, among other chaperones, on the membrane of tumor cells [28][29][30][31]. Membrane exposure of HSP70 was indeed observed on A431 and scc-U8 cells treated with mild NB-PDT, although it was more evident on the high EGFR-expressing cells at the early timepoint studied (Figure 2a,b).…”

Section: Discussionmentioning

confidence: 99%

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

Hernández

Angelier

D’Ondes

et al. 2020

Cancers

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M.L.A.); a.dimaggio@students.uu.nl (A.D.M.); Y.Yu@uu.nl (Y.Y.)Abstract: Nanobody-targeted photodynamic therapy (NB-PDT) has been recently developed as a more tumor-selective approach rather than conventional photodynamic therapy (PDT). NB-PDT uses nanobodies that bind to tumor cells with high affinity, to selectively deliver a photosensitizer, i.e., a chemical which becomes cytotoxic when excited with light of a particular wavelength. Conventional PDT has been reported to be able to induce immunogenic cell death, characterized by the exposure/release of damage-associated molecular patterns (DAMPs) from dying cells, which can lead to antitumor immunity. We explored this aspect in the context of NB-PDT, targeting the epidermal growth factor receptor (EGFR), using high and moderate EGFR-expressing cells. Here we report that, after NB-PDT, the cytoplasmic DAMP HSP70 was detected on the cell membrane of tumor cells and the nuclear DAMP HMGB1 was found in the cell cytoplasm. Furthermore, it was shown that NB-PDT induced the release of the DAMPs HSP70 and ATP, as well as the pro-inflammatory cytokines IL-1β and IL-6. Conditioned medium from high EGFR-expressing tumor cells treated with NB-PDT led to the maturation of human dendritic cells, as indicated by the upregulation of CD86 and MHC II on their cell surface, and the increased release of IL-12p40 and IL-1β. Subsequently, these dendritic cells induced CD4+ T cell proliferation, accompanied by IFNγ release. Altogether, the initial steps reported here point towards the potential of NB-PDT to stimulate the immune system, thus giving this selective-local therapy a systemic reach.Despite being a selective and controllable treatment against tumor cells, therapies known to be considerably aggressive towards all tissues (i.e., chemo-and radiotherapy) are still the mainstream clinical practice, when it comes to combat cancer [5]. Some current barriers for the establishment of PDT in routine practice are the required technology, complex dosimetry, limited tissue penetration of light and/or PS, lack of tumor specificity and prolonged skin photosensitivity [1,5]. Efforts have been put into improving the selectivity of PDT towards the cancer cells by using antibodies, an approach which is now in phase II clinical trial (NCT02422979) [6]. Conjugation of a water-soluble PS (IRDye700DX) to an antibody allows the PS to be specifically delivered to cancer cells overexpressing a certain antigen on the cell membrane. In this manner, two levels of specificity are established: the delivery of PS to target-expressing cells and the local application of light at the tumor site.Another strategy to render PDT more tumor-selective is nanobody-targeted PDT (NB-PDT), which also utilizes the near-infrared PS IRDye700DX. In this case, however, a nanobody is used to provide the first level of specificity [7,8]. NBs are the smallest binding domains found in nature (~15 kDa) and consist uniquely of the variable domain of heavy chain antibodies present in Camelids [9]. The use of a NB for PDT brings a ...

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Section: Discussionmentioning

confidence: 99%

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

Hernández

Angelier

D’Ondes

et al. 2020

Cancers

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“…Mice which were systemically depleted of DCs showed 90% of disease recurrence compared to only 20% in mice which received PDT treatment only [36]. Furthermore, other reports support the involvement of DCs in the response to PDT as evidenced by enhanced maturation and activation as well as increased secretion of proinflammatory cytokines after treatment [37,38,39,40]. …”

Section: Pdt and Innate Immunitymentioning

confidence: 99%

“…Zheng et al found a decrease of Treg induction in vitro and in vivo in response to stimulation/treatment with DC which had been pulsed with PDT-treated Lewis lung carcinoma cells (LLC). This was accompanied by a significant inhibition of tumor growth upon challenge with live LLC cells [40]. In a clinical setting, blood analysis of patients with esophageal squamous cell carcinoma demonstrated that PDT with the PS Photofrin ® abolished the suppressive function of peripheral Treg, but had no effect on Treg numbers [72].…”

Section: Pdt and Adaptive Immunitymentioning

confidence: 99%

Boosting Tumor-Specific Immunity Using PDT

Maeding

Verwanger

Krammer

2016

Cancers

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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.

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“…In turn, NK cell adoptive therapy can improve the tumor-killing effect of PDT. 124 This result is interesting for researchers who are struggling with the numerous side effects of anti-CD47 monoclonal antibody in tumor immunotherapy. 107 Macrophages maintain organic homeostasis by removing abnormal cells and perform important roles in tumorigenesis and progression.…”

Section: Recent Advance Of Nanoparticle-based Pdtmentioning

confidence: 97%

“…A report suggested that PDT targeting of the cellular endoplasmic reticulum can induce endoplasmic reticulum stress via ROS production to suppress "do not eat me" signals (CD47 and Treg cells) while enhancing "eat me" signals (CRT and HSPs) and activate downstream antitumor immune response. 124 This result is interesting for researchers who are struggling with the numerous side effects of anti-CD47 monoclonal antibody in tumor immunotherapy.…”

Section: Recent Advance Of Nanoparticle-based Pdtmentioning

confidence: 97%

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

Hou

Tao

Pang

et al. 2018

Intl Journal of Cancer

186

123

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Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly killing tumor cells through heat and reactive oxygen species, PTT and PDT can also induce various antitumor effects. In particular, the resultant massive tumor cell death after PTT and PDT triggers immune responses, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. The antitumor effects can be enhanced by immune checkpoint blockage therapy. This article reviewed the recent advances of nanoparticle-based PTT and PDT, summarized the studies on nanoparticle-based photothermal and photodynamic immunotherapies in vitro and in vivo, and discussed challenges and future research directions.

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Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy

Cited by 81 publications

References 35 publications

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

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

Boosting Tumor-Specific Immunity Using PDT

Nanoparticle‐based photothermal and photodynamic immunotherapy for tumor treatment

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