Induction of Systemic Neutrophil Response in Mice by Photodynamic Therapy of Solid Tumors¶

Cecić, Ivana; Parkins, C. S.; Korbelik, Mladen

doi:10.1562/0031-8655(2001)074<0712:iosnri>2.0.co;2

Cited by 75 publications

(51 citation statements)

References 32 publications

(39 reference statements)

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“…Another type of myeloid cell, most likely monocytes, invaded the tumour 2 hours after PDT. Cecic et al 90 found that pronounced neutrophilia developed rapidly after Photofrin or mTHPC-mediated PDT of mice with SCCVII or EMT6 mammary carcinomas. Neutrophilia was also observed after PDT treatment of normal dorsal skin, but not in the footpad of tumour-free mice.…”

Section: Neutrophil Recruitment and The Production Of Il6mentioning

confidence: 99%

Photodynamic therapy and anti-tumour immunity

2006

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Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.The principle of photodynamic therapy (PDT) was first proposed over 100 years ago 1 . A recent review in Nature Reviews Cancer by Rakesh Jain and colleagues described some of the historical milestones in the development of PDT as a cancer treatment2. Many of the photosensitizers (PSs) that have been studied since PDT was first proposed are based on a porphyrin-like nucleus 3 . PSs function as catalysts when they absorb visible light and then convert molecular oxygen to a range of highly reactive oxygen species (ROS). The ROS that are produced during PDT have been shown to destroy tumours by multifactorial mechanisms4 , 5 (FIG. 1). PDT has a direct affect on cancer cells, producing cell death by necrosis and/or apoptosis 6 . PDT also has an affect on the tumour vasculature, whereby illumination and ROS production causes the shutdown of vessels and subsequently deprives the tumour of oxygen and nutrients 7,8 . Finally, PDT also has a significant effect on the immune system 9-11 , which can be either immunostimulatory or immunosuppressive.Most of the commonly used cancer therapies are immunosuppressive. Chemotherapy and ionizing radiation delivered at doses sufficient to destroy tumours are known to be toxic to the bone marrow, which is the source of all cells of the immune system, and neutropaenia and other forms of myelosuppression are often the dose-limiting toxicity of these therapies. However, it should be noted that low doses of either ionizing radiation12 , 13 or chemotherapy14 can have immunostimulatory effects, including the induction of heat-shock © 2006 Nature Publishing Group Correspondence to M.R.H. Hamblin@helix.mgh.harvard.edu. Competing interests statementThe authors declare no competing financial interests. DATABASES NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2010 September 6. Published in final edited form as:Nat Rev Cancer. 2006 July ; 6(7): 535-545. doi:10.1038/nrc1894. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript proteins 15 . Less well known is the fact that major surgery can also have an immunosuppressive effect that leads to a significant diminution of lymphocyte and natural killer (NK) cell function 16 . The ideal cancer therapy would not only destroy the primary tumour, but at the same time trigger the immune system to recognize, track down and destroy any remaining tumour cells, be they at or near the site of the primary tumour or distant microm...

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Section: Neutrophil Recruitment and The Production Of Il6mentioning

confidence: 99%

Photodynamic therapy and anti-tumour immunity

2006

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“…A particularly immunogenic type of cell death is necrosis, where a lot of DAMPs are released, but apoptotic and stressed cells contribute as well, especially if the extent of damage is large and/or rapidly peaks upon PDT application (Korbelik 2006). DAMPs activate the complement system and the resident innate immune cells such as macrophages, dendritic cells and mastocytes, which in turn orchestrate acute inflammation and recruit other innate immune subsets such as neutrophils and natural killer (NK) cells (Cecic et al 2001;Korbelik 2006;Kousis et al 2007). Several processes that follow promote tumour cell death; these include the activation of macrophages and neutrophils to promote apoptosis and/or necrosis by release of proinflammatory cytokines (such as IL-1β, TNF and IL-6), the complement system-induced damage to endothelial cells, and direct recognition and elimination of tumour cells by NK cells.…”

Section: Pdt and The Immune System Pdt-mediated Immune Responses In Cmentioning

confidence: 99%

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

2017

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Photodynamic therapy (PDT) combines a photosensitiser, light and molecular oxygen to induce oxidative stress that can be used to kill pathogens, cancer cells and other highly proliferative cells. There is a growing number of clinically approved photosensitisers and applications of PDT, whose main advantages include the possibility of selective targeting, localised action and stimulation of the immune responses. Further improvements and broader use of PDT could be accomplished by designing new photosensitisers with increased selectivity and bioavailability. Porphyrin-based photosensitisers with amphiphilic properties, bearing one or more positive charges, are an effective tool in PDT against cancers, microbial infections and, most recently, autoimmune skin disorders. The aim of the review is to present some of the recent examples of the applications and research that employ this specific group of photosensitisers. Furthermore, we will highlight the link between their structural characteristics and PDT efficiency, which will be helpful as guidelines for rational design and evaluation of new PSs.

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“…However, several studies have indicated that local PDT treatment of tumours can result in wide-spread effects including systemic neutrophilia (Cecic et al, 2001), induction of acute-phase proteins (Cecic et al, 2001;Gollnick et al, 2003), increased circulating levels of complement proteins (Cecic et al, 2006) and systemic release of pro-inflammatory cytokines (Nseyo et al, 1990;Ziolkowski et al, 1996;de Vree et al, 1997;Cecic and Korbelik, 2002;Gollnick et al, 2003;Yom et al, 2003), all of which indicate the presence of a systemic inflammatory response. Subsequent studies showed that local PDT treatment of murine tumours results in the induction of anti-tumour immunity and resistance to subsequent tumour challenge (reviewed in Canti et al, 2002;Castano et al, 2006).…”

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confidence: 99%

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

et al. 2007

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Cancer survival rates decrease in the presence of disseminated disease. However, there are few therapies that are effective at eliminating the primary tumour while providing control of distant stage disease. Photodynamic therapy (PDT) is an FDA-approved modality that rapidly eliminates local tumours, resulting in cure of early disease and palliation of advanced disease. Numerous preclinical studies have shown that local PDT treatment of tumours enhances anti-tumour immunity. We hypothesised that enhancement of a systemic anti-tumour immune response might control the growth of tumours present outside the treatment field. To test this hypothesis we delivered PDT to subcutaneous (s.c.) tumours of mice bearing both s.c. and lung tumours and monitored the growth of the untreated lung tumours. Our results demonstrate that PDT of murine tumours provided durable inhibition of the growth of untreated lung tumours. The inhibition of the growth of tumours outside the treatment field was tumour-specific and dependent on the presence of CD8 þ T cells. This inhibition was accompanied by an increase in splenic anti-tumour cytolytic activity and by an increase in CD8 þ T cell infiltration into untreated tumours. Local PDT treatment led to enhanced anti-tumour immune memory that was evident 40 days after tumour treatment and was independent of CD4 þ T cells. CD8 þ T cell control of the growth of lung tumours present outside the treatment field following PDT was dependent upon the presence of natural killer (NK) cells. These results suggest that local PDT treatment of tumours lead to induction of an anti-tumour immune response capable of controlling the growth of tumours outside the treatment field and indicate that this modality has potential in the treatment of distant stage disease.

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Induction of Systemic Neutrophil Response in Mice by Photodynamic Therapy of Solid Tumors¶

Cited by 75 publications

References 32 publications

Photodynamic therapy and anti-tumour immunity

Photodynamic therapy and anti-tumour immunity

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

CD8+ T cell-mediated control of distant tumours following local photodynamic therapy is independent of CD4+ T cells and dependent on natural killer cells

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