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https://www.readbyqxmd.com/read/28536278/immune-checkpoint-blockade-immunogenic-chemotherapy-or-ifn-%C3%AE-blockade-boost-the-local-and-abscopal-effects-of-oncolytic-virotherapy
#1
Laetitia Fend, Takahiro Yamazaki, Christelle Remy, Catherine Fahrner, Murielle Gantzer, Virginie Nourtier, Xavier Préville, Eric Quéméneur, Oliver Kepp, Julien Adam, Aurélien Marabelle, Jonathan M Pitt, Guido Kroemer, Laurence Zitvogel
Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK(-)RR(-)-Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8(+) T cells, and immune cell infiltrate in the tumor could be reprogrammed towards a higher ratio of effector T cells to regulatory CD4(+) T cells...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28533222/fractionated-radiation-therapy-stimulates-anti-tumor-immunity-mediated-by-both-resident-and-infiltrating-polyclonal-t-cell-populations-when-combined-with-pd1-blockade
#2
Simon J Dovedi, Eleanor J Cheadle, Amy Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik Yusko, Catherine Sanders, Marissa Vignali, Ryan Emerson, Harlan Robins, Robert W Wilkinson, Jamie Honeychurch, Timothy Illidge
Purpose: Radiotherapy (RT) is a highly effective anti-cancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. RT is known to enhance tumor immunogenicity; however, the contribution and mechanisms of RT induced immune responses are unknown. <p>Experimental Design: The impact of low-dose fractionated RT (5 x 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing (NGS) of the T-cell receptor (TCR)-repertoire...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28522277/-immunotherapy-and-radiotherapy
#3
S Bockel, D Antoni, É Deutsch, F Mornex
Radiotherapy, primarily known for its cytotoxic effect on the tumor cells, via the induction of DNA damages, has the ability to induce a systemic antitumoral response. By an immunologic cell death, tumor cells exposed to radiation release a large amount of neoantigenes and pro-inflammatory mediators, acting as an in situ vaccine, resulting in an tumor regression within the primary irradiated site, but also in the distant "out of field" secondary tumors. However, this phenomenon is extremly rare with radiotherapy alone, suggesting that the radiation-induced antitumor immunity is not sufficient for overcoming the tumor's and its microenvironnement immunosuppressing effect...
May 15, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28512270/abscopal-effect-propitious-or-pernicious
#4
Sachin C Sarode, Nikunj Maniyar, Gargi S Sarode, Shankargouda Patil
Recent advances in the field of radiation biology have increased our knowledge of cellular responses to radiation and microenvironmental disseminations through radiation at molecular level.
May 1, 2017: Journal of Contemporary Dental Practice
https://www.readbyqxmd.com/read/28501459/-cancer-radiotherapy-and-immune-system
#5
J P Nesseler, D Peiffert, G Vogin, P Nickers
Novel paradigms emerge in oncology today. Systemic treatments are more effective and diversified along with an increased life expectancy in oligometastatic patients. Stereotactic radiotherapy using hypofractionation opens new perspectives for local tumour control. The area of radiobiology has expanded with integration of tumour microenvironment in which radiation-induced inflammation mediators and immune system play a major role. Immunity checkpoints inhibitors experience a major development. This rapidly evolving field seems involved in the abscopal effects, especially when radiation is combined with checkpoints inhibitors, as demonstrated in numerous preclinical studies and several clinical trials...
May 10, 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28475423/investigating-the-abscopal-effects-of-radioablation-on-shielded-bone-marrow-in-rodent-models-using-multimodality-imaging
#6
Solmaz F Afshar, Janice A Zawaski, Taeko Inoue, David A Rendon, Arthur W Zieske, Jyotinder N Punia, Omaima M Sabek, M Waleed Gaber
The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery...
May 5, 2017: Radiation Research
https://www.readbyqxmd.com/read/28447024/following-the-preclinical-data-leveraging-the-abscopal-effect-more-efficaciously
#7
Wilfred Ngwa, Zi Ouyang
Radiotherapy is employed in the treatment of over 50% of cancer patients. However, this therapy approach is limited to mainly treating localized disease. In 1953, Mole described the remarkable abscopal effect, whereby, localized radiotherapy of a patient's primary tumor might engender regression of cancer at distant sites, which were not irradiated. Current consensus is that if the abscopal effect can be efficaciously leveraged, it would transform the field of radiation oncology, extending the use of radiotherapy to treatment of both localized and metastatic disease...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28440500/indirect-effects-of-x-irradiation-on-proliferation-and-osteogenic-potential-of-bone-marrow-mesenchymal-stem-cells-in-a-local-irradiated-rat-model
#8
Ruilian Sun, Guoying Zhu, Jianping Wang, Ling Tong, Jianglong Zhai
Cancer survivors after radiotherapy may suffer a variety of bone‑related adverse side effects, including radioactive osteoporosis and fractures. Localized irradiation is a common treatment modality for malignancies. Recently, a series of reactions and injuries called indirect effects (remote changes in bone when other parts of the body are irradiated) have been reported on the indirect irradiated area of bone tissue after radiotherapy. To address this issue, we developed a rat localized irradiation model...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28409192/can-local-radiotherapy-and-il-12-synergise-to-overcome-the-immunosuppressive-tumor-microenvironment-and-allow-in-situ-tumor-vaccination
#9
Gaël Deplanque, Keyvan Shabafrouz, Michel Obeid
The abscopal effect, which is the spontaneous regression of tumors or metastases outside the radiation field, occurs rarely in cancer patients. Interestingly, radiotherapy (RT) triggers an immunogenic cell death (ICD) that is able to generate tumor-specific cytotoxic CD8(+) T cells that are efficient in killing cancer cells. The key question is: why is this "abscopal effect" so uncommon in cancer patients treated with RT? Most probably, the main reason may be related to the highly immunosuppressive tumor microenvironment of well-established tumors that constantly antagonizes the anti-tumor immune responses triggered by RT...
April 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28396751/an-abscopal-effect-in-a-case-of-concomitant-treatment-of-locally-and-peritoneally-recurrent-gastric-cancer-using-adoptive-t-cell-immunotherapy-and-radiotherapy
#10
Hiro Sato, Yoshiyuki Suzuki, Yuya Yoshimoto, Shin-Ei Noda, Kazutoshi Murata, Yosuke Takakusagi, Atsushi Okazaki, Tetsuo Sekihara, Takashi Nakano
The mechanism of abscopal effect is becoming clear by the progress of cancer immunology. A 54-year-old male with recurrent gastric cancer presented an abscopal effect after radiotherapy with concurrent adoptive T-cell immunotherapy (immunoradiotherapy). Immunoradiotherapy has potential to induce abscopal effect by strengthening systemic antitumor immunity even in recurrent cancer.
April 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28357914/short-review-of-potential-synergies-of-immune-checkpoint-inhibition-and-radiotherapy-with-a-focus-on-hodgkin-lymphoma-radio-immunotherapy-opens-new-doors
#11
REVIEW
Christian Baues, Maike Trommer-Nestler, Karolina Jablonska, Paul J Bröckelmann, Max Schlaak, Michael von Bergwelt-Baildon, Andreas Engert, Robert Semrau, Simone Marnitz, Sebastian Theurich
Radiotherapy is an established local treatment in patients with various malignancies. Systemic responses following local irradiation have been described as abscopal effects. Modern cancer immunotherapy with immune checkpoint inhibitors has shown impressive response rates and prolongation of survival even in heavily pretreated patients with advanced solid malignancies and lymphomas. Radiotherapy has been shown to modulate immune response, and its application in the context of immune checkpoint inhibition has recently evolved into an active field of research...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28352658/priming-is-key-to-effective-incorporation-of-image-guided-thermal-ablation-into-immunotherapy-protocols
#12
Matthew T Silvestrini, Elizabeth S Ingham, Lisa M Mahakian, Azadeh Kheirolomoom, Yu Liu, Brett Z Fite, Sarah M Tam, Samantha T Tucci, Katherine D Watson, Andrew W Wong, Arta M Monjazeb, Neil E Hubbard, William J Murphy, Alexander D Borowsky, Katherine W Ferrara
Focal therapies play an important role in the treatment of cancers where palliation is desired, local control is needed, or surgical resection is not feasible. Pairing immunotherapy with such focal treatments is particularly attractive; however, there is emerging evidence that focal therapy can have a positive or negative impact on the efficacy of immunotherapy. Thermal ablation is an appealing modality to pair with such protocols, as tumors can be rapidly debulked (cell death occurring within minutes to hours), tumor antigens can be released locally, and treatment can be conducted and repeated without the concerns of radiation-based therapies...
March 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28348554/barriers-to-radiation-induced-in-situ-tumor-vaccination
#13
REVIEW
Erik Wennerberg, Claire Lhuillier, Claire Vanpouille-Box, Karsten A Pilones, Elena García-Martínez, Nils-Petter Rudqvist, Silvia C Formenti, Sandra Demaria
The immunostimulatory properties of radiation therapy (RT) have recently generated widespread interest due to preclinical and clinical evidence that tumor-localized RT can sometimes induce antitumor immune responses mediating regression of non-irradiated metastases (abscopal effect). The ability of RT to activate antitumor T cells explains the synergy of RT with immune checkpoint inhibitors, which has been well documented in mouse tumor models and is supported by observations of more frequent abscopal responses in patients refractory to immunotherapy who receive RT during immunotherapy...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28344743/the-abscopal-effect-of-radiation-therapy-what-is-it-and-how-can-we-use-it-in-breast-cancer
#14
REVIEW
Zishuo I Hu, Heather L McArthur, Alice Y Ho
The abscopal effect refers to the ability of localized radiation to trigger systemic antitumor effects. Over the past 50 years, reports on the abscopal effect arising from conventional radiation have been relatively rare. However, with the continued development and use of immunotherapy strategies incorporating radiotherapy with targeted immunomodulators and immune checkpoint blockade, the abscopal effect is becoming increasingly relevant in less immunogenic tumors such as breast cancer. Here, we review the mechanism of the abscopal effect, the current preclinical and clinical data, and the application of the abscopal effect in designing clinical trials of immunotherapy combined with radiotherapy in breast cancer...
2017: Current Breast Cancer Reports
https://www.readbyqxmd.com/read/28291902/review-of-the-mechanisms-involved-in-the-abscopal-effect-and-future-directions-with-a-focus-on-thymic-carcinoma
#15
Paul Lesueur, François Chevalier, Dinu Stefan, Jean-Louis Habrand, Delphine Lerouge, Radj Gervais
The abscopal effect is a rare phenomenon in radiotherapy, leading to impressive tumor regression outside the radiotherapy field. In this article we describe the occurrence of a postradiotherapy abscopal effect in an 89-year-old patient suffering from a metastatic neuroendocrine large-cell thymic carcinoma, the first case of the abscopal effect related to a thymic carcinoma reported in the literature. Along with the description of this case, we discuss and review the main potential mechanisms of bystander and abscopal effects in solid tumors so as to enable clinicians to identify and control these effects more resourcefully in the age of immunotherapy and stereotactic radiotherapy...
March 3, 2017: Tumori
https://www.readbyqxmd.com/read/28275377/impact-of-particle-irradiation-on-the-immune-system-from-the-clinic-to-mars
#16
REVIEW
Rodrigo Fernandez-Gonzalo, Sarah Baatout, Marjan Moreels
Despite the generalized use of photon-based radiation (i.e., gamma rays and X-rays) to treat different cancer types, particle radiotherapy (i.e., protons and carbon ions) is becoming a popular, and more effective tool to treat specific tumors due to the improved physical properties and biological effectiveness. Current scientific evidence indicates that conventional radiation therapy affects the tumor immunological profile in a particular manner, which in turn, might induce beneficial effects both at local and systemic (i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28267380/abscopal-effect-of-metastatic-pancreatic-cancer-after-local-radiotherapy-and-granulocyte-macrophage-colony-stimulating-factor-therapy
#17
Fang Shi, Xin Wang, Feifei Teng, Li Kong, Jinming Yu
The role of immunotherapy in combination with traditional treatment regime in improving the survival of cancer patients has attracted more and more attention. Especially the abscopal effect that describes the phenomenon of localized radiotherapy leading to regression of distant unirradiated tumors and the role of enhanced radiotherapy-induced immunogenic cell death and activation of immune system have become a focus of the studies. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known a powerful stimulator of the generation, migration and activation of antigen presenting cells such as dendritic cells (DC) and macrophages...
March 4, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28236557/photons-radiobiological-issues-related-to-the-risk-of-second-malignancies
#18
Loredana G Marcu
Photons are widely used in radiotherapy and while they are low LET radiation, can still pose a risk in developing second malignant neoplasms (SMN). Due to the physics of photons that allow distribution of energy outside the target volume, out-of-field irradiation is an important component of SMN risk assessment. The epidemiological evidence supporting this risk should be augmented with radiobiological justifications for a better understanding of the underlying processes. There are several factors that impact second cancer risk which can be analysed from a radiobiological perspective: age at irradiation, type of irradiated tissue, irradiated volume, treatment technique, previous irradiation/radiological investigations...
February 21, 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/28230241/results-of-a-phase-ii-open-label-non-comparative-study-of-intralesional-pv-10-followed-by-radiotherapy-for-the-treatment-of-in-transit-or-metastatic-melanoma
#19
Matthew Foote, Tavis Read, Janine Thomas, Michael Wagels, Bryan Burmeister, B Mark Smithers
BACKGROUND: In-transit and recurrent dermal or subcutaneous melanoma metastases represent a significant burden of advanced disease. Intralesional Rose Bengal can elicit tumor selective ablation and a T-cell mediated abscopal effect in untreated lesions. A subset of patients in a phase II trial setting received external beam radiotherapy to their recurrent lesions with complete or partial response and no significant acute radiation reaction. METHODS: An open-label, single-arm phase II study was performed to assess the efficacy and safety of PV-10 followed by hypofractionated radiotherapy...
February 23, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28222111/a-meta-analysis-of-the-abscopal-effect-in-preclinical-models-is-the-biologically-effective-dose-a-relevant-physical-trigger
#20
Raffaella Marconi, Silvia Strolin, Gianluca Bossi, Lidia Strigari
BACKGROUND: Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence...
2017: PloS One
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