Photodynamic therapy downregulates the function of regulatory T cells in patients with esophageal squamous cell carcinoma

Reginato, Eleonora; Lindenmann, Jörg; Langner, Cord; Schweintzger, Nina A.; Bambach, Isabella; Smolle‐Jüttner, Freyja Maria; Wolf, Peter

doi:10.1039/c4pp00186a

Cited by 34 publications

(28 citation statements)

References 59 publications

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“…This clinical effect of low‐dose PDT on antitumor immunity is in line with preclinical studies showing that low‐dose PDT enhanced antitumor immunity more effectively than high‐dose PDT (5,62). PDT was also shown to reduce immunosuppression, through reduction in Tregs, in invasive esophageal squamous cell carcinoma (ESCC) patients (8).…”

Section: Components Of Pdt: Photosensitizer Light and Molecular Oxygenmentioning

confidence: 99%

Photodynamic Therapy and Immunity: An Update

Falk-Mahapatra

Gollnick

2020

Photochem & Photobiology

129

110

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Dr. Thomas Dougherty and his Oncology Foundation of Buffalo were the first to support my (S.O.G.) research into the effects of photodynamic therapy (PDT) on the host immune system. The small grant I was awarded in 2002 launched my career as an independent researcher; at the time, there were few studies on the importance of the immune response on the efficacy of PDT and no studies demonstrating the ability of PDT to enhance antitumor immunity. Over the last decades, the interest in PDT as an enhancer of antitumor immunity and our understanding of the mechanisms by which PDT enhances antitumor immunity have dramatically increased. In this review article, we look back on the studies that laid the foundation for our understanding and provide an update on current advances and therapies that take advantage of PDT enhancement of immunity.

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Section: Components Of Pdt: Photosensitizer Light and Molecular Oxygenmentioning

confidence: 99%

Photodynamic Therapy and Immunity: An Update

Falk-Mahapatra

Gollnick

2020

Photochem & Photobiology

129

110

View full text Add to dashboard Cite

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“…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]. Taken together, these studies indicate effects of PDT on Treg, which have to be elucidated in order to harness the potential of PDT to break tumor-promoting immune suppression.…”

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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“…Therefore, in addition to having less effector T cells due to increased Pc 4 uptake and PDT-dependent apoptosis, there would be a higher ratio of Treg:Teff cells and a net suppressive environment which would result in a more effective suppression of a responding effector T cell response. Whether this will be demonstrable in autoinflammatory disorders and cancer remains to be seen, as a decrease in Treg in situ in esophageal cancer following PDT with Photofrin was not observed (30). Extensive investigations using various PDT photosensitizers have previously revealed preferential uptake of photosensitizers by 1.)…”

Section: Discussionmentioning

confidence: 99%

Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death

Soler

Ohtola

Sugiyama

et al. 2016

Photochem Photobiol Sci

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Photodynamic therapy (PDT) is an emerging treatment for malignant and inflammatory dermal disorders. Photoirradiation of the silicon phthalocyanine (Pc) 4 photosensitizer with red light generates singlet oxygen and other reactive oxygen species to induce cell death. We previously reported that Pc 4-PDT elicited cell death in lymphoid-derived (Jurkat) and epithelial-derived (A431) cell lines in vitro, and furthermore that Jurkat cells were more sensitive than A431 cells to treatment. In this study, we examined the effectiveness of Pc 4-PDT on primary human CD3+ T cells in vitro. Fluorometric analyses of lysed T cells confirmed the dose-dependent uptake of Pc 4 in non-stimulated and stimulated T cells. Flow cytometric analyses measuring annexin V and propidium iodide (PI) demonstrated a dose-dependent increase of T cell apoptosis (6.6–59.9%) at Pc 4 doses ranging from 0–300 nM. Following T cell stimulation through the T cell receptor using a combination of anti-CD3 and anti-CD28 antibodies, activated T cells exhibited increased susceptibility to Pc 4-PDT-induced apoptosis (10.6–81.2%) as determined by Pc 4 fluorescence in each cell, in both non-stimulated and stimulated T cells, Pc 4 uptake increased with Pc 4 dose up to 300 nM as assessed by flow cytometry. The mean fluorescence intensity (MFI) of Pc 4 uptake measured in stimulated T cells was significantly increased over the uptake of resting T cells at each dose of Pc 4 tested (50, 100, 150 and 300nM, p<0.001 between 50 and 150nM, n=8). Treg uptake was diminished relative to other T cells. Cutaneous T cell lymphoma (CTCL) T cells appeared to take up somewhat more Pc 4 than normal resting T cells at 100 and 150nm Pc 4. Confocal imaging revealed that Pc 4 localized in cytoplasmic organelles, with approximately half of the Pc 4 co-localized with mitochondria in T cells. Thus, Pc 4-PDT exerts an enhanced apoptotic effect on activated CD3+ T cells that may be exploited in targeting T cell-mediated skin diseases, such as cutaneous T cell lymphoma (CTCL) or psoriasis.

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Photodynamic therapy downregulates the function of regulatory T cells in patients with esophageal squamous cell carcinoma

Cited by 34 publications

References 59 publications

Photodynamic Therapy and Immunity: An Update

Photodynamic Therapy and Immunity: An Update

Boosting Tumor-Specific Immunity Using PDT

Activated T cells exhibit increased uptake of silicon phthalocyanine Pc 4 and increased susceptibility to Pc 4-photodynamic therapy-mediated cell death

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