• Aminolevulinic acid
• Antitumor effect
• Extracorporeal blood circulation
• Hematological malignancies
• Photodynamic therapy

• Aminolevulinic Acid/pharmacology
• Animals
• Photochemotherapy/methods
• Rats
• Protoporphyrins/pharmacology
• Photosensitizing Agents/pharmacology
• Glioma/drug therapy
• Glioma/therapy
• Glioma/pathology
• Cell Line, Tumor
• Calreticulin/metabolism
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/drug effects
• Male
• Humans

• Otsuka Medical Devices Co., Ltd, Japan

• Humans
• Neoplasms/therapy
• Neoplasms/drug therapy
• Photosensitizing Agents/chemistry
• Photosensitizing Agents/therapeutic use
• Photosensitizing Agents/pharmacology
• Phototherapy/methods
• Animals
• Photochemotherapy

• cancer immunotherapy
• immune checkpoint inhibitors
• immunogenic cell death
• photodynamic therapy
• tumor microenvironment

• Photochemotherapy/methods
• Tumor Microenvironment/immunology
• Tumor Microenvironment/drug effects
• Humans
• Neoplasms/therapy
• Neoplasms/immunology
• Immunotherapy/methods
• Nanoparticles
• Animals
• Photosensitizing Agents/therapeutic use
• Combined Modality Therapy
• Nanomedicine/methods

• Fundação de Amparo à Pesquisa do Estado de São Paulo
• Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital, Generalitat Valenciana
• Agencia Estatal de Investigación
• European Regional Development Fund
• Conselho Nacional de Desenvolvimento Científico e Tecnológico
• Universitat de València

• anti-tumor immunity
• cancer
• clinical trials
• photodynamic therapy

• Humans
• Photochemotherapy/methods
• Adjuvants, Immunologic/therapeutic use
• Photosensitizing Agents/therapeutic use
• Neoplasms/drug therapy
• Neoplasms/pathology
• Immunotherapy/methods

• Cancer
• OSCC
• Oral
• Photodynamic

• Humans
• Photosensitizing Agents/therapeutic use
• Photochemotherapy
• Mouth Neoplasms/drug therapy
• Combined Modality Therapy

• cancer vaccine
• photodynamic therapy
• radiovaccination

Photodynamic therapy (PDT)-based cancer vaccines are shown to be more effective modalities for treating cancer in animal models compared to other methods used to generate cancer cell-derived vaccines. The higher efficacy seems to stem from the generation of cell membrane nanovesicles or fragments that carry both cancer cell-specific antigens and high surface content of damage-associated molecular pattern (DAMP) molecules induced by oxidative stress. To develop more effective cancer vaccines in this direction, we explored the generation of cancer vaccines by applying different sources of oxidative stress on cancer cell cultures followed by spontaneous release or filter extrusions to produce cancer cell-derived DAMP-expressing nanovesicles. Through an in-vitro test based on the co-culture of cancer cells and macrophages, it was found that the nanovesicle vaccines generated by H2O2 are as effective as those generated by PDT in diminishing cancer cell culture masses, providing a simpler way to manufacture vaccines. In addition, the nanovesicle vaccines produced by filter extrusion are as potent as those produced by spontaneous release, rendering a more stable way for vaccine production.

Cancer is a major threat to human health because of its high mortality, easy recurrence, strong invasion, and metastasis. Photodynamic therapy (PDT) is a promising minimally invasive treatment for tumor. Compared with traditional treatment methods, PDT is less invasive and does not easily damage normal tissues. Most of the effects of this treatment are due to the direct effects of singlet oxygen together with reactive oxygen species. PDT can provide the source of active oxygen for the Fenton reaction, which enhances ferroptosis and also improves the efficacy of PDT in antitumor therapy. Additionally, in contrast to chemotherapy and radiotherapy, PDT has the effect of stimulating the immune response, which can effectively induce immunogenic cell death (ICD) and stimulate immunity. PDT is an ideal minimally invasive treatment method for tumors. In this paper, according to the characteristics of anti-tumor immunity of PDT, some tumor treatment strategies of PDT combined with anti-tumor immunotherapy are reviewed.

The induction and direction of stem cell differentiation into needed cell phenotypes is the central pillar of tissue engineering for repairing damaged tissues or organs. Conventionally, a special recipe of chemical factors is formulated to achieve this purpose for each specific target cell type. In this work, it is demonstrated that the combination of extrinsic photobiomodulation and collagen-covered microislands could be used to induce differentiation of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) with the differentiation direction dictated by the specific island topography without use of chemical factors. Both neurogenic differentiation and adipogenic differentiation could be attained with a rate surpassing that using chemical factors. Application of this method to other cell types is possible by utilizing microislands with a pattern tailored particularly for each specific cell type, rendering it a versatile modality for initiating and guiding stem cell differentiation.

• Antigen
• Cancer
• Immunotherapy
• PDT
• Peptide
• Photodynamic therapy
• SLP
• T cells
• Tumor
• Vaccination

• Cancer Vaccines/therapeutic use
• Humans
• Immunotherapy/methods
• Neoplasms/drug therapy
• Photochemotherapy/methods
• Vaccination

• breast cancer
• cell line
• nanoparticles
• nanotechnology
• photodynamic therapy
• photosensitizer

• cancer immunotherapy
• mouse SCCVII tumor
• phagocytic receptors
• photodynamic therapy-generated vaccine
• therapeutic vaccine
• tumor cell vaccine

• Adjuvants
• Biomaterials
• Cancer treatment
• Imaging
• Immunotherapy
• Nanoparticles
• Theranostic
• Tumor
• Vaccines

• Animals
• Cancer Vaccines/administration & dosage
• Disease Models, Animal
• Drug Carriers/chemistry
• Humans
• Immunologic Factors/administration & dosage
• Immunotherapy/methods
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/therapy
• Theranostic Nanomedicine/methods

• R01 CA204552 NCI NIH HHS
• R01 CA206069 NCI NIH HHS
• R01 CA210192 NCI NIH HHS

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.

• clinical trials
• immune checkpoint inhibition
• immunotherapy
• murine models
• photodynamic therapy
• photothermal therapy
• radiation therapy

• Immune-Related diseases
• Immunomodulation
• Photodynamic therapy

• Humans
• Neoplasms/drug therapy
• Oxygen
• Photochemotherapy/methods
• Photosensitizing Agents/therapeutic use

• CCR7
• CD8(+) T cell priming
• Dendritic cell migration
• Photochemical internalization
• Skin-inflammation

• Animals
• Antineoplastic Agents, Phytogenic/administration & dosage
• Antineoplastic Agents, Phytogenic/pharmacokinetics
• Antineoplastic Agents, Phytogenic/therapeutic use
• Breast Neoplasms/drug therapy
• Disease Models, Animal
• Female
• Humans
• Paclitaxel/administration & dosage
• Paclitaxel/pharmacokinetics
• Paclitaxel/therapeutic use
• Photochemotherapy/methods
• Prodrugs/administration & dosage
• Prodrugs/pharmacokinetics
• Prodrugs/therapeutic use
• Rats
• Rats, Inbred F344

• R01 GM113940 NIGMS NIH HHS
• R01GM113940 NIGMS NIH HHS

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.

• immunogenic cell death
• immunomodulation
• innate and adaptive immunity
• photodynamic therapy

• Caspase-1
• Immunoregulatory cells
• N-dihydrogalactochitosan
• PTT vaccine
• Phtothermal therapy (PTT)
• Tumor control

• Cell death
• Endoplasmic reticulum stress
• Immunogenic cell death and anti-tumor immunity
• Integrated stress response
• Nrf2 antioxidant pathway
• Oxidative stress
• Photodynamic therapy

• Photodynamic therapy
• immune therapy
• melanoma
• neoangiogenesis
• oxidative stress
• photosensitizer
• signaling pathway.

• Cherenkov radiation
• X-ray induced photodynamic therapy
• nanoparticles
• photodynamic therapy
• radiation therapy
• scintillation

• Luminescence
• Nanoparticles/chemistry
• Nanoparticles/ultrastructure
• Photochemotherapy
• Radiation
• X-Rays

• R01 EB022596 NIBIB NIH HHS
• R01 NS093314 NINDS NIH HHS

• Autophagy inhibitor
• Immunotherapy
• Osteosarcoma
• PD-L1
• Photodynamic therapy

• drugs
• human papilloma virus (HPV)
• prophylaxis
• therapy
• vaccines

• Adolescent
• Antiviral Agents/therapeutic use
• Condylomata Acuminata/immunology
• Condylomata Acuminata/prevention & control
• Drug Design
• Drug Development
• Female
• Humans
• Immunization Programs
• Male
• Oropharyngeal Neoplasms/immunology
• Oropharyngeal Neoplasms/prevention & control
• Papillomaviridae/physiology
• Papillomavirus Infections/drug therapy
• Papillomavirus Infections/immunology
• Papillomavirus Vaccines/immunology
• Uterine Cervical Neoplasms/immunology
• Uterine Cervical Neoplasms/prevention & control
• Vaccination

Photodynamic therapy, one of the most promising minimally invasive treatments, has received increasing focus in tumor therapy research, which has been widely applied in treating superficial tumors. Three basic factors - photosensitizer, the light source, and oxidative stress - are responsible for tumor cell cytotoxicity. However, due to insufficient luminous flux and peripheral tissue damage, the utilization of photodynamic therapy is facing a huge limitation in deep tumor therapy. Osteosarcoma is the typical deep tumor, which is the most commonly occurring malignancy in children and adolescents. Despite developments in surgery, high risks of the amputation still threatens the health of osteosarcoma patients. In this review, we summarize recent developments in the field of photodynamic therapy and specifically PDT research in OS treatment modalities. In addition, we also provide some novel suggestions, which could potentially be a breakthrough in PDT-induced OS therapies. PDT has the potential to become an effective therapy while the its limitations still present when applied on the treatment of OS or other types of deep tumors. Thus, more researches and studies in the field are required.

• immunotherapy
• nanotechnology
• osteosarcoma
• photodynamic
• target therapy

Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.

• cancer
• clinical trials
• future
• photodynamic therapy
• preclinical
• treatment outcome

• 677582 European Research Council

Myeloid regulatory cells (Mregs) are, together with regulatory T cells (Tregs), a dominant effector population responsible for restriction of the duration and strength of antitumor immune response. Photodynamic therapy (PDT) and cancer vaccines generated by PDT are modalities whose effectiveness in tumor destruction is closely dependent on the associated antitumor immune response. The present study investigated whether the immunodepletion of granulocytic Mregs in host mice by anti-GR1 antibody would improve the response of tumors to PDT or PDT vaccines in these animals. Anti-GR1 administration immediately after Temoporfin-PDT of mouse SCCVII tumors abrogated curative effect of PDT. The opposite effect, increasing PDT-mediated tumor cure-rates was attained by delaying anti-GR1 treatment to 1 h post PDT. With PDT vaccines, multiple anti-GR1 administrations (days 0, 4, and 8 post vaccination) improved the therapy response with SCCVII tumors. The results with PDT suggest that neutrophils (boosting antitumor effect of this therapy) that are engaged immediately after photodynamic light treatment are within one hour replaced with a different myeloid population, presumably Mregs that hampers the therapy-mediated antitumor effect. Anti-GR1 antibody, when used with optimal timing, can improve the efficacy of both PDT of tumors in situ and PDT-generated cancer vaccines.

• Mregs
• anti-GR1 antibody
• cancer vaccines
• photodynamic therapy

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.

• antitumor immunity, regulatory T cells
• dendritic cells
• memory
• photodynamic tumor therapy
• tumor-specific immunity

• oral cancers
• photodynamic therapy
• precancer
• topical treatment
• tumor vaccine

• acid ceramidase inhibitor LCL521
• immunoregulatory cells
• photodynamic therapy
• photodynamic therapy-generated cancer vaccine

• apoptosis
• autophagy
• lysosomes
• mitochondria
• photosensitizer
• porphyrin

• R01 CA023378 NCI NIH HHS

The main task of cancer vaccines is to deliver tumor-specific antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy (PDT)-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These findings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.

• Antitumor immune response
• Photodynamic therapy-generated vaccines
• Cell death
• Endoplasmic reticulum stress response
• Reticular unfolded proteins response
• Damage-associated molecular patterns
• Immunogenic cell death

The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called “damage-associated molecular patterns” (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.

• anti-tumor immunity
• immunogenicity
• immunotherapy
• molecular medicine
• oncoimmunology
• patient prognosis
• translational medicine

Photodynamic therapy (PDT)-generated cancer vaccine represents an attractive potential application of PDT, therapeutic modality destroying targeted lesions by localized photooxidative stress. Since immunoregulatory cell activity has become recognized as a major obstacle to effective cancer immunotherapy, the present study examined their participation in the therapeutic effect of PDT cancer vaccine. Following protocols from previous studies, mouse with squamous cell carcinoma SCCVII tumors were vaccinated by SCCVII cells treated by PDT and response monitored by tumor size measurement. The effects of low-dose cyclophosphamide (50 mg/kg) and all-trans retinoic acid (ATRA) on the numbers of Tregs and myeloid-derived suppressor cells (MDSCs) were determined by antibody staining followed by flow cytometry, while their impact on PDT vaccine therapy was evaluated by monitoring changes in tumor responses. Cyclophosphamide effectively reduced the numbers of Tregs, which became elevated following PDT vaccine treatment, and this resulted in an increase in the vaccine’s effectiveness. A similar benefit for the therapy outcome with PDT vaccine was attained by ATRA treatment. The activities of Tregs and MDSCs thus have a critical impact on therapy outcome with PDT vaccine and reducing their numbers substantially improves the vaccine’s effectiveness.

• all-trans retinoic acid (ATRA)
• cancer vaccines
• cyclophosphamide
• immunoregulatory cells
• photodynamic therapy

• Cholangiocarcinoma
• Fluorescence kinetics
• Foscan(®) PDT
• mTHPC