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Photodynamic therapy: Immunology and clinical oncology
Abstracts / Photodiagnosis and Photodynamic Therapy 17 (2017) A4–A78
References [1] [2] [3] [4]
N. Engl. J. Med. 365 (2011) 395–409. H. Kato, J. Natl. Compr. Cancer Netw. 10 (2) (2012) S3–S8. Y. Kato, H. Nakamura, M. Nomura, et al., Clin. Transl. Med. 4 (2015) 24. H. Kato, T. Okunaka, T. Tsuchida, et al., Diagn. Ther. Endosc. 6 (1999) 9–16.
PDT in immunology Oral OI-063 Photodynamic therapy: Immunology and clinical oncology
http://dx.doi.org/10.1016/j.pdpdt.2017.01.067
R. Allison
Oral OP-062
21st Century Oncology, Editor in Chief, Elsevier Journal Photodiagnosis and Photodynamic Therapy, United States
Surgery and intraoperative photodynamic therapy for thoracic malignancies K.A. Cengel 1,∗ , T.M. Busch 1 , S. Albelda 1 , J. Friedberg 2 , S. Singhal 1 , C.B. Simone 2 1 University of Pennsylvania, Departments of Radiation Oncology, Medicine and Surgery, Philadelphia, PA, USA 2 University of Maryland, Departments of Radiation Oncology and Surgery, Baltimore, MD, USA
The goal of surgery in the multimodal treatment of pleural malignancies such as malignant pleural mesothelioma (MPM) or Non-small cell lung cancer with pleural spread (p-NSCLC) is to achieve a macroscopic compete resection (MCR). We have investigated the use of intraoperative photodynamic therapy to reduce the rate of local recurrence following MCR using a variety of photosensitizers, including porfimer sodium and HPPH. With lung sparing MCR and intraoperative PDT, patients with locally advanced, epithelial MPM experience median overall progression free and overall survival of 13 and 36 months, respectively. Similarly, patients with p-NSCLC experience median progression free and overall survival of 10 and 23 months, respectively. The results with MCR and PDT are highly encouraging. Nevertheless, a subset of patients treated with this approach experience aggressive local or systemic relapse of pleural disease within the first 12 months. In this study, we combine analysis of clinical data and pre-clinical models to examine the hypothesis that cytokine signaling stimulated by the surgical resection can impair the efficacy of PDT. Patients who have undergone surgery followed by HPPH mediated PDT experience distinct patterns of inflammatory cytokine release. Patients experiencing a significant increase in pro-inflammatory cytokines plasma levels from surgery prior to PDT appear to exhibit a greater degree of systemic toxicity and earlier recurrences than patients who did not experience a proinflammatory reaction to surgery. This correlates with increased baseline expression of inflammatory markers including STAT3. We have modeled this phenomenon in mice with syngeneic MPM tumors in which the tumor is incompletely resected and PDT is then performed. These experiments reveal that surgery can impair the efficacy of PDT, but that this effect is reversed by pretreatment of animals with non-steroidal anti-inflammatory agents. In vitro experiments suggest that a least one mechanism behind this phenomenon is the ability of surgically induced cytokines to promote cancer cell survival following PDT. Taken together, these results demonstrate that PDT can be safely and effectively adapted to treat the entire pleural surface and that PDT combined with multimodality, surgically based therapy demonstrates remarkably good patient outcomes. However, pro-inflammatory cytokines produced during surgical resection can have a negative impact on the efficacy of intraoperative PDT. http://dx.doi.org/10.1016/j.pdpdt.2017.01.068
A31
Photodynamic therapy in oncology is clinically simple, which has allowed for widespread use. Yet this simplicity masks the complex biological and physical interactions and transformations associated with this treatment. This talk will highlight the immunological activities initiated by the photodynamic reaction and the downstream results of this therapy. Clinical maneuvers that may enhance outcome and minimize non target morbidity will also be described. http://dx.doi.org/10.1016/j.pdpdt.2017.01.069 Oral OI-064 Enhancement of anti-tumor immunity by PDT: Mechanisms and exploitation S.O. Gollnick Roswell Park Cancer Institute, Buffalo, NY, USA Photodynamic therapy (PDT) enhancement of anti-tumor immunity has been demonstrated in both clinical and pre-clinical settings. PDT enhancement of anti-tumor immunity appears to be due to several factors including stimulation of immunogenic cell death, induction of acute inflammation, release of tumor specific antigens and activation of dendritic cells resulting in stimulation of tumor specific T cells. In addition PDT can eliminate suppressive immune cells within the tumor microenvironment. Pre-clinical studies have shown that the augmentation of anti-tumor immunity by PDT can result in both local and systemic control of disease, providing rationale for use of PDT in an adjuvant setting. While encouraging, recent studies have shown that modalities that stimulate anti-tumor immunity can also lead to immune escape by tumors via simultaneous enhancement of immune checkpoint molecules such as PDL1. These studies suggest that PDT enhancement of anti-tumor immunity may be heightened by blockade of immune checkpoint molecules. Data supporting each of these concepts will be presented in this overview seminar. http://dx.doi.org/10.1016/j.pdpdt.2017.01.070 Oral OI-065 The impact of photodynamic-immunotherapy on the antitumor immunity: Local effects and systemic consequences J.M. Dabrowski 1,∗ , B. Pucelik 1 , L.B. Rocha 2 , M.M. Pereira 3 , L.G. Arnaut 2,3 1
Faculty of Chemistry, Jagiellonian University, Krakow, Poland 2 Luzitin SA, Coimbra, Portugal 3 Chemistry Department, University of Coimbra, Portugal Phodynamic-immunotherapy is an anticancer strategy that leads to destruction of treated tumor and stimulation of the host
References [1] [2] [3] [4]
N. Engl. J. Med. 365 (2011) 395–409. H. Kato, J. Natl. Compr. Cancer Netw. 10 (2) (2012) S3–S8. Y. Kato, H. Nakamura, M. Nomura, et al., Clin. Transl. Med. 4 (2015) 24. H. Kato, T. Okunaka, T. Tsuchida, et al., Diagn. Ther. Endosc. 6 (1999) 9–16.
PDT in immunology Oral OI-063 Photodynamic therapy: Immunology and clinical oncology
http://dx.doi.org/10.1016/j.pdpdt.2017.01.067
R. Allison
Oral OP-062
21st Century Oncology, Editor in Chief, Elsevier Journal Photodiagnosis and Photodynamic Therapy, United States
Surgery and intraoperative photodynamic therapy for thoracic malignancies K.A. Cengel 1,∗ , T.M. Busch 1 , S. Albelda 1 , J. Friedberg 2 , S. Singhal 1 , C.B. Simone 2 1 University of Pennsylvania, Departments of Radiation Oncology, Medicine and Surgery, Philadelphia, PA, USA 2 University of Maryland, Departments of Radiation Oncology and Surgery, Baltimore, MD, USA
The goal of surgery in the multimodal treatment of pleural malignancies such as malignant pleural mesothelioma (MPM) or Non-small cell lung cancer with pleural spread (p-NSCLC) is to achieve a macroscopic compete resection (MCR). We have investigated the use of intraoperative photodynamic therapy to reduce the rate of local recurrence following MCR using a variety of photosensitizers, including porfimer sodium and HPPH. With lung sparing MCR and intraoperative PDT, patients with locally advanced, epithelial MPM experience median overall progression free and overall survival of 13 and 36 months, respectively. Similarly, patients with p-NSCLC experience median progression free and overall survival of 10 and 23 months, respectively. The results with MCR and PDT are highly encouraging. Nevertheless, a subset of patients treated with this approach experience aggressive local or systemic relapse of pleural disease within the first 12 months. In this study, we combine analysis of clinical data and pre-clinical models to examine the hypothesis that cytokine signaling stimulated by the surgical resection can impair the efficacy of PDT. Patients who have undergone surgery followed by HPPH mediated PDT experience distinct patterns of inflammatory cytokine release. Patients experiencing a significant increase in pro-inflammatory cytokines plasma levels from surgery prior to PDT appear to exhibit a greater degree of systemic toxicity and earlier recurrences than patients who did not experience a proinflammatory reaction to surgery. This correlates with increased baseline expression of inflammatory markers including STAT3. We have modeled this phenomenon in mice with syngeneic MPM tumors in which the tumor is incompletely resected and PDT is then performed. These experiments reveal that surgery can impair the efficacy of PDT, but that this effect is reversed by pretreatment of animals with non-steroidal anti-inflammatory agents. In vitro experiments suggest that a least one mechanism behind this phenomenon is the ability of surgically induced cytokines to promote cancer cell survival following PDT. Taken together, these results demonstrate that PDT can be safely and effectively adapted to treat the entire pleural surface and that PDT combined with multimodality, surgically based therapy demonstrates remarkably good patient outcomes. However, pro-inflammatory cytokines produced during surgical resection can have a negative impact on the efficacy of intraoperative PDT. http://dx.doi.org/10.1016/j.pdpdt.2017.01.068
A31
Photodynamic therapy in oncology is clinically simple, which has allowed for widespread use. Yet this simplicity masks the complex biological and physical interactions and transformations associated with this treatment. This talk will highlight the immunological activities initiated by the photodynamic reaction and the downstream results of this therapy. Clinical maneuvers that may enhance outcome and minimize non target morbidity will also be described. http://dx.doi.org/10.1016/j.pdpdt.2017.01.069 Oral OI-064 Enhancement of anti-tumor immunity by PDT: Mechanisms and exploitation S.O. Gollnick Roswell Park Cancer Institute, Buffalo, NY, USA Photodynamic therapy (PDT) enhancement of anti-tumor immunity has been demonstrated in both clinical and pre-clinical settings. PDT enhancement of anti-tumor immunity appears to be due to several factors including stimulation of immunogenic cell death, induction of acute inflammation, release of tumor specific antigens and activation of dendritic cells resulting in stimulation of tumor specific T cells. In addition PDT can eliminate suppressive immune cells within the tumor microenvironment. Pre-clinical studies have shown that the augmentation of anti-tumor immunity by PDT can result in both local and systemic control of disease, providing rationale for use of PDT in an adjuvant setting. While encouraging, recent studies have shown that modalities that stimulate anti-tumor immunity can also lead to immune escape by tumors via simultaneous enhancement of immune checkpoint molecules such as PDL1. These studies suggest that PDT enhancement of anti-tumor immunity may be heightened by blockade of immune checkpoint molecules. Data supporting each of these concepts will be presented in this overview seminar. http://dx.doi.org/10.1016/j.pdpdt.2017.01.070 Oral OI-065 The impact of photodynamic-immunotherapy on the antitumor immunity: Local effects and systemic consequences J.M. Dabrowski 1,∗ , B. Pucelik 1 , L.B. Rocha 2 , M.M. Pereira 3 , L.G. Arnaut 2,3 1
Faculty of Chemistry, Jagiellonian University, Krakow, Poland 2 Luzitin SA, Coimbra, Portugal 3 Chemistry Department, University of Coimbra, Portugal Phodynamic-immunotherapy is an anticancer strategy that leads to destruction of treated tumor and stimulation of the host