Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status

Strigari, Lidia; Mancuso, Mariateresa; Ubertini, Valentina; Soriani, A.; Giardullo, Paola; Benassi, Marcello; D'Alessio, Daniela; Leonardi, Simona; Soddu, Silvia; Bossi, Gianluca

doi:10.3109/09553002.2014.874608

Cited by 54 publications

(43 citation statements)

References 15 publications

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“…Xie et al reported that the phosphorylation of p53 could result in increased radiosensitivity and the inhibition of tumor reproduction [26]. Strigari et al also demonstrated that p53-dependent signals might be responsible for the abscopal effect in RT to sterilize nonirradiated tumor cells through a proapoptotic pathway [27]. These outcomes were also compatible with our results that the overexpression of p53 enhanced the radiation-induced G2/M phase arrest of OC3 cells.…”

Section: Discussionsupporting

confidence: 92%

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

Liu

2016

Oncotarget

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Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo. An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.

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Section: Discussionsupporting

confidence: 92%

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

Liu

2016

Oncotarget

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“…With the exception of immunogenic cell death, this is still largely unexplored terrain. Two preclinical models suggest p53 as a key mediator for abscopal effects [38, 39]. In clinical research, a couple of the mentioned papers also explored individual markers in abscopal responses.…”

Section: Discussionmentioning

confidence: 99%

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

Reynders

Illidge

Siva

et al. 2015

Cancer Treatment Reviews

505

405

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Background Recently, immunologic responses to localized irradiation are proposed as mediator of systemic effects after localized radiotherapy (called the abscopal effect). Here, we give an overview of both preclinical and clinical data about the abscopal effect in particular and link them with the immunogenic properties of radiotherapy. Methods We searched Medline and Embase with the search term “abscopal” from 1960 until July, 2014. Only papers that cover radiotherapy in an oncological setting were selected and only if no concurrent cytotoxic treatment was given. Targeted immune therapy was allowed. Results Twenty-three case reports, one retrospective study and 13 preclinical papers were selected. Eleven preclinical papers used a combination of immune modification and radiotherapy to achieve abscopal effects. Patient age range (28 to 83 years) and radiation dose (median total dose 32 Gy) varied. Fractionation size ranged from 1,2 Gy to 26 Gy. Time to documented abscopal response ranged between less than one and 24 months, with a median reported time of 5 months. Once an abscopal response was achieved, a median time of 13 months went by before disease progression occurred or the reported follow-up ended (range 3–39 months). Conclusion Preclinical data points heavily towards a strong synergy between radiotherapy and immune treatments. Recent case reports already illustrate that such a systemic effect of radiotherapy is possible when enhanced by targeted immune treatments. However, several issues concerning dosage, timing, patient selection and toxicity need to be resolved before the abscopal effect can become clinically relevant.

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“…In our opinion, the most rational explanation of the abscopal effect is the concept of ICD. One of the major effects ICD can unleash an effective immune response is induction of a strong “danger signal” generated by damaged tissue under endoplasmic reticulum stress [22]. Dying tumor cells succumbing to ICD induce danger signals called “alarmins” that have immunogenic properties.…”

Section: Discussionmentioning

confidence: 99%

Treatment of osteosarcoma with microwave thermal ablation to induce immunogenic cell death

Geng

Zhang

et al. 2014

Oncotarget

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Microwave ablation (MWA) has been used as a classical hyperthermic ablation method for decades with the intention to induce direct killing of tumor cells or modulation of tumor architecture. The purpose of this study was to explore whether MWA induced tumor cell death could generate an immunogenic source of tumor antigens and elicit tumor-specific immune responses, taking an alternative antitumor effects. Three kinds of osteosarcoma cell lines, respectively derived from mice, rats and human, were selected as ablation models. In vitro and in situ tumor ablation were both performed to detect the “damage-associated molecular patterns” (DAMPs) exposure level. Active ablated products vaccination resulted in complete protection in both mouse and rat tumor-bearing models, which was mediated primarily by vaccine-elicited CD8+ T cells. These effector cells functioned by releasing IFN-γ and TNF-α in the presence of target cells, which may trigger FasL-directed cell apoptosis. These data suggest that MWA-processed osteosarcoma cells could be applied to generate specific antitumor effects, especially for in situ ablation. Hence, MWA could be used in combination with immunotherapy, especially for patients who have failed chemotherapy or who have limited treatment options.

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Abscopal effect of radiation therapy: Interplay between radiation dose and p53 status

Abstract: We suggest that the interplay between delivered dose and p53 status might help to sterilize out-of-field tumour cells.

Cited by 54 publications

References 15 publications

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant

Treatment of osteosarcoma with microwave thermal ablation to induce immunogenic cell death

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