development-an-innovative-led-based-illumination-device-for-vitro

Development of an Innovative LED-based Illumination Device for <em>In Vitro</em> Application of Photodynamic Therapy with Rose Bengal

This article describes a new photodynamic therapy (PDT) device for evaluating the efficacy of Rose Bengal (RB)-mediated PDT in vitro. The device, called ...

UNIVERSITY OF LILLE

Glioblastoma (GBM) is characterized by marked proliferation, major infiltration, and poor prognosis. Despite current treatments, including surgery, radiation oncology, and chemotherapy, the overall median survival is 15 mo and the progression-free survival is 7 to 8 mo. Because of systematic relapse of the tumor, the improvement of local control remains an issue. In this context, photodynamic therapy (PDT) may offer a new treatment modality for GBM.

INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial.

Colorectal cancer (CRC) remains the most cancer type related to chronic inflammation; however, the mechanisms that link inflammation to CRC development and progression are still poorly understood. Our study aimed to investigate one of the prominent inflammatory response in cancers, iNOS/NO system. In this regard, we evaluated the link between the iNOS/NO system and CRC progression, its relation with the host immune responses and its response to cetuximab combined with chemotherapy. We found that the nitrite levels were nearly twice as high in metastatic CRC plasma and culture supernatants from PBMCs and tumor explants compared with those without metastases and healthy controls. Interestingly, we showed that the highest iNOS expression and NO levels are present in the damaged CRC tissues that have highest leukocyte infiltration. Our findings highlight the implication of iNOS/NO system in tissue alteration and leukocyte invasion. Thus, we observed imbalance between effector/memory T cell markers and Treg transcription factor (Foxp3). Accordingly, we detected higher IFNγ and T-bet expression levels in colorectal tumor tissues at early stage. In contrast, consistent with iNOS and Foxp3 expression, TGFβ, CTLA-4 and IL-10 were significantly related to the tumor stage progression. Furthermore, our study revealed that Cetuximab combined with chemotherapy treatment markedly down-regulates iNOS/NO system as well as IL-10 and TGFβ levels. Altogether, we conclude that cetuximab can potentiate the efficacy of chemotherapy, particularly by iNOS/NO system and immunosuppressive cytokines modulation. Thus, we suggest that iNOS/NO system may represent an attractive candidate biomarker for monitoring CRC progression, malignity and response to therapy.

Aberrant up-regulation of iNOS/NO system is correlated with an increased abundance of Foxp3 cells and reduced effector/memory cell markers expression during colorectal cancer: immunomodulatory effects of cetuximab combined with chemotherapy.

Surgical management of peritoneal metastases raises the problem of the theoretical spread of the entire peritoneal surface. Intraperitoneal photodynamic therapy (IntraPDT) has been limited by the lack of specificity of photosensitizers (PS) and difficulties to bring light into the abdominal cavity. Recent data in ovarian cancer may give development opportunities for IntraPDT. Intraperitoneal PDT could be an option but the level of evidence of research in this topic must increase. Our opinion is that the most important is to have a realistic idea of what we can objectively expect from PDT and the feasibility of its daily application. At the time of personalized medicine, it is mandatory to select population eligible for a targeted PS administration and who could benefit from the process. The design of a specific PS for each subtype of cancers seems essential to avoid side effects on healthy tissue. On the contrary, our progress on lighting solutions can be beneficial for all patients with an indication of IntraPDT regardless of the origin of PM. A common lighting system developed for all cancers eligible for IntraPDT could be adapted with light source of specific wavelength to activate dedicated PS.

A global approach for the development of photodynamic therapy of peritoneal metastases regardless of their origin.

Nasopharyngeal carcinoma (NPC) is a malignant tumour of the head and neck affecting localised regions of the world, with the highest rates described in Southeast Asia, Northern Africa, and Greenland. Its high morbidity rate is linked to both late-stage diagnosis and unresponsiveness to conventional anti-cancer treatments. Multiple aetiological factors have been described including environmental factors, genetics, and viral factors (Epstein Barr Virus, EBV), making NPC treatment that much more complex. The most common forms of NPCs are those that originate from the epithelial tissue lining the nasopharynx and are often linked to EBV infection. Indeed, they represent 75-95% of NPCs in the low-risk populations and almost 100% of NPCs in high-risk populations. Although conventional surgery has been improved with nasopharyngectomy's being carried out using more sophisticated surgical equipment for better tumour resection, recent findings in the tumour microenvironment have led to novel treatment options including immunotherapies and photodynamic therapy, able to target the tumour and improve the immune system. This review provides an update on the disease's aetiology and the future of NPC treatments with a focus on therapies activating T cell immunity.

Novel Therapies Boosting T Cell Immunity in Epstein Barr Virus-Associated Nasopharyngeal Carcinoma.

The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.

Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patient.

Immunosuppressive-drugs are needed after solid organ transplantation to prevent allograft rejection but induce severe side effects. Understanding the alloimmune response is critical to modulate it and to achieve graft operational tolerance. The role of regulatory T cells and tolerogenic dendritic cells (Tol-DCs) is undoubtedly essential in tolerance induction. Tacrolimus is considered as the cornerstone of immunosuppression in solid organ transplantation. mTOR inhibitor such as rapamycin are thought to induce tolerance and are used as anticancer drugs in several cancers. The aim of this study was to better understand the effect of these immunosuppressive drugs on the differentiation, maturation and function of human monocyte derived dendritic cells (DCs).

Modulatory effect of rapamycin and tacrolimus on monocyte-derived dendritic cells phenotype and function.

Photodynamic Therapy (PDT) relies on local or systemic administration of a light-sensitive dye, called photosensitizer, to accumulate into the target site followed by excitation with light of appropriate wavelength and fluence. This photo-activated molecule reacts with the intracellular oxygen to induce selective cytotoxicity of targeted cells by the generation of reactive oxygen species. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-associated mortality worldwide, has insufficient treatment options available. In this review, we discuss the mechanism and merits of PDT along with its recent developments as an anti-cancerous therapy. We also highlight the application of this novel therapy for diagnosis, visualization, and treatment of HCC. We examine the underlying challenges, some pre-clinical and clinical studies, and possibilities of future studies associated with PDT. Finally, we discuss the mechanism of an active immune response by PDT and thereafter explored the role of PDT in the generation of anti-tumor immune response in the context of HCC, with an emphasis on checkpoint inhibitor-based immunotherapy. The objective of this review is to propose PDT as a plausible adjuvant to existing therapies for HCC, highlighting a feasible combinatorial approach for HCC treatment.

Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies.

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied.

Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite new treatments, the HCC rate remains important, making it necessary to develop novel therapeutic strategies. Photodynamic therapy (PDT) using a Rose-Bengal (RB) photosensitizer (RB-PDT) could be a promising approach for liver tumor treatment. However, the lack of standardization in preclinical research and the diversity of illumination parameters used make comparison difficult across studies. This work presents and characterizes a novel illumination device based on one green light-emitting diode (CELL-LED-550/3) dedicated to an in vitro RB-PDT. The device was demonstrated to deliver a low average irradiance of 0.62 mW/cm over the 96 wells of a multi-well plate. Thermal characterization showed that illumination does not cause cell heating and can be performed inside an incubator, allowing a more rigorous assessment of cell viability after PDT. An in vitro cytotoxic study of the RB-PDT on an HCC cell line (HepG2) demonstrated that RB-PDT induces a significant decrease in cell viability: almost all the cells died after a light dose irradiation of 0.3 J/cm using 75 µM of RB (<10% of viability). In conclusion, the RB-PDT could be a therapeutic option to treat unresectable liver lesions and subclinical disease remaining in the post-resection tumor surgical margin.

Photodynamic Therapy Using a Rose-Bengal Photosensitizer for Hepatocellular Carcinoma Treatment: Proposition for a Novel Green LED-Based Device for In Vitro Investigation.

Efficient 5-ALA-photodynamic therapy in nasopharyngeal carcinoma induces an immunoactivation mediated by tumoral extracellular vesicles and associated with immunogenic cell death.

Cerebrovascular reserve (CVR) is a key physiological mechanism allowing the brain to adapt to fluctuating perfusion, particularly relevant in the management of neurovascular disorders such as idiopathic (iMM) and syndromic moyamoya (sMM). Although 99mTc-HMPAO SPECT with acetazolamide is commonly used for CVR assessment, it faces limitations including low spatial resolution, artifacts, and variability in interpretation. This study primarily aims to evaluate a novel, semiautomated, and more objective method for interpreting HMPAO SPECT in CVR assessment. As a secondary objective, the method is applied to a cohort of patients who underwent revascularization surgery for iMM or sMM.

Article	Year
INtraoperative photoDYnamic Therapy for GliOblastomas (INDYGO): Study Protocol for a Phase I Clinical Trial. Neurosurgery\| PubMed ID: 30053213	2019
Aberrant up-regulation of iNOS/NO system is correlated with an increased abundance of Foxp3 cells and reduced effector/memory cell markers expression during colorectal cancer: immunomodulato... Inflammopharmacology\| PubMed ID: 30680650	2019
A global approach for the development of photodynamic therapy of peritoneal metastases regardless of their origin. Photodiagnosis and photodynamic therapy\| PubMed ID: 32061747	2020
Novel Therapies Boosting T Cell Immunity in Epstein Barr Virus-Associated Nasopharyngeal Carcinoma. International journal of molecular sciences\| PubMed ID: 32560253	2020
Combination of High Dose Hypofractionated Radiotherapy with Anti-PD1 Single Dose Immunotherapy Leads to a Th1 Immune Activation Resulting in a Complete Clinical Response in a Melanoma Patien... International journal of molecular sciences\| PubMed ID: 32942768	2020
Modulatory effect of rapamycin and tacrolimus on monocyte-derived dendritic cells phenotype and function. Immunobiology\| PubMed ID: 33278711	2021
Could Photodynamic Therapy Be a Promising Therapeutic Modality in Hepatocellular Carcinoma Patients? A Critical Review of Experimental and Clinical Studies. Cancers\| PubMed ID: 34680325	2021
Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynam... Pharmaceuticals (Basel, Switzerland)\| PubMed ID: 36015182	2022
Photodynamic Therapy Using a Rose-Bengal Photosensitizer for Hepatocellular Carcinoma Treatment: Proposition for a Novel Green LED-Based Device for In Vitro Investigation. Biomedicines\| PubMed ID: 39335633	2024
Efficient 5-ALA-photodynamic therapy in nasopharyngeal carcinoma induces an immunoactivation mediated by tumoral extracellular vesicles and associated with immunogenic cell death. Cancer communications (London, England)\| PubMed ID: 39749695	2025
Toward Semiautomated Analysis of Cerebrovascular Reserve: Enhancing Objective Comparisons Using 99mTc-HMPAO SPECT With Acetazolamide in Moyamoya. Neurosurgery\| PubMed ID: 40891845	2025

Nadira Delhem

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