Radiation, inflammation and the immune response in cancer

McKelvey, Kelly; Hudson, Amanda L.; Back, Michael; Eade, Thomas; Diakos, Connie I.

doi:10.1007/s00335-018-9777-0

Cited by 141 publications

(119 citation statements)

References 198 publications

(264 reference statements)

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“…87 Indeed, ionizing radiation has been linked to immunogenic cancer cell death through radiation-induced release of DAMPs, which initiate and promote inflammatory responses mediated by activated dendritic cells presenting tumor-specific antigens to prime cytotoxic T cells. 88 External beam radiation doses above 12-18 Gy have been shown to activate the expression of DNA exonuclease Trex1, to degrade the DNA in the cytosol of irradiated cancer cells and to prevent activation of STING downstream of the type-I interferon pathway. 89 Similar to the effects of c and b radiation, irradiation with the a-particle-emitting radionuclide 213 Bi complexed to bovine serum albumin induced a release of DAMPs when inoculated in vitro on murine adenocarcinoma MC38 cells, mimicking an in situ vaccination approach.…”

Section: Immunostimulatory Effect Of Ttcsmentioning

confidence: 99%

Advances in Precision Oncology: Targeted Thorium-227 Conjugates As a New Modality in Targeted Alpha Therapy

Hagemann

Wickstroem

Hammer

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Targeted alpha therapy (TAT) offers the potential for the targeted delivery of potent a-particle-emitting radionuclides that emit high linear energy transfer radiation. This leads to a densely ionizing radiation track over a short path. Localized radiation induces cytotoxic, difficult-to-repair, clustered DNA double-strand breaks (DSBs). To date, radium-223 (223 Ra) is the only TAT approved for the treatment of patients with metastatic castration-resistant prostate cancer. Thorium-227 (227 Th), the progenitor nuclide of 223 Ra, offers promise as a wider-ranging alternative due to the availability of efficient chelators, such as octadentate 3,2-hydroxypyridinone (3,2-HOPO). The 3,2-HOPO chelator can be readily conjugated to a range of targeting moieties, enabling the generation of new targeted thorium-227 conjugates (TTCs). This review provides a comprehensive overview of the advances in the preclinical development of TTCs for hematological cancers, including CD22-positive B cell cancers and CD33-positive leukemia, as well as for solid tumors overexpressing renal cell cancer antigen CD70, membrane-anchored glycoprotein mesothelin in mesothelioma, prostate-specific membrane antigen in prostate cancer, and fibroblast growth factor receptor 2. As the mechanism of action for TTCs is linked to the formation of DSBs, the authors also report data supporting combinations of TTCs with inhibitors of the DNA damage response pathways, including those of the ataxia telangiectasia and Rad3-related protein, and poly-ADP ribose polymerase. Finally, emerging evidence suggests that TTCs induce immunogenic cell death through the release of danger-associated molecular patterns. Based on encouraging preclinical data, clinical studies have been initiated to investigate the safety and tolerability of TTCs in patients with various cancers.

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Section: Immunostimulatory Effect Of Ttcsmentioning

confidence: 99%

Advances in Precision Oncology: Targeted Thorium-227 Conjugates As a New Modality in Targeted Alpha Therapy

Hagemann

Wickstroem

Hammer

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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“…It has been reported that IR with different dose per fraction schemes could change the tumor immune microenvironment (32,33) and create "in situ vaccine" to induce an effective abscopal effect on remote tumors (off target) (34,35). This study, using two HCC mouse models, demonstrated that hypofractionated IR was more effective to create the abscopal effect with a high dose per fraction in the same 40-Gy total dose, that is, ≥4 Gy/fraction.…”

Section: Discussionmentioning

confidence: 79%

Hypofractionated Irradiation Suppressed the Off-Target Mouse Hepatocarcinoma Growth by Inhibiting Myeloid-Derived Suppressor Cell-Mediated Immune Suppression

et al. 2020

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“…Within the inflammatory microenvironment induced by irradiation, these cells are universally present [19], but in this study, it was unclear whether RvE1 regulates the expressions of IL-2, IL-6, and TNF-α in the inner ear via this mechanism. This question is worthy of study in the future.…”

Section: Discussionmentioning

confidence: 81%

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response

Zhang

Niu

et al. 2020

Preprint

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Background In addition to the direct effects of irradiation, the induced inflammatory response may play an important role in the damage to the inner ear caused by radiotherapy for the treatment of head and neck cancers. Resolvin E1 has anti-inflammatory activity, acting by reducing neutrophil infiltration and proinflammatory cytokine expression. Therefore, in this study we sought to confirm whether the inflammation induced by irradiation was involved in damage to the inner ear after radiotherapy and to investigate the protective effect and underlying mechanism of resolvin E1 using mouse models.Methods A dose of resolvin E1 was delivered by intraperitoneal injection to mice before irradiation.Changes in the auditory brainstem response, relative balance ability, inner ear morphology and the expression levels of proinflammatory cytokines in the inner ear were analyzed on days 7 and 14 after irradiation and compared among three experimental groups.Results Morphological analysis of the inner ear showed severe damage to the cochlea and vestibule after irradiation. In contrast, damage to the cochlea and vestibule was significantly reduced in the resolvin E1-pretreated group, which nonetheless remained damaged compared to the wild-type group. Proinflammatory cytokines also showed expression patterns matching the morphological observations.Conclusions We believe that the inflammation induced by irradiation is involved in the damage to the inner ear caused by radiotherapy, and that resolvin E1 reduces the damage caused by irradiation to the inner ear by regulating the induced inflammatory response.Therefore in this study, a mouse experiment was designed to investigate these problems and the potential mechanism of RvE1 in protecting against irradiation-induced damage to the inner ear. Materials And Methods Animals and Study GroupsC57BL/6 mice weighing 25-27 grams were purchased from the Experimental Animal Center of Shandong University for this experiment, and all animal procedures in this study were approved by the Ethics Committee of the Second Hospital of Shandong University.Study Groups: 36 mice were randomly divided into three groups: a wild type group (WT), X-ray irradiation group (Rad), and RvE1-pretreated X-ray irradiation group (Rad+RvE1). On days 7 and 14 after irradiation, six mice in each group were sacrificed for experimental analysis. The irradiation groups were irradiated with 20 Gy in one fraction to the inner ear. This dose was determined according to the results of a preliminary experiment, to ensure robust survival of all experimental mice along with detectable damage to inner ear functions. Before irradiation, 10% chloral hydrate was used for enterocoelia anesthesia at a dose of 1,000 mg/kg without any signs of peritonitis after administration. On the day of the experiments, 1 μg RvE1 was administered to the mice via intraperitoneal injection 30 minutes before irradiation, according to a previous report [11,16].After the experimental mice were anesthetized and placed in a soundproof room, the collection ...

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Radiation, inflammation and the immune response in cancer

Cited by 141 publications

References 198 publications

Advances in Precision Oncology: Targeted Thorium-227 Conjugates As a New Modality in Targeted Alpha Therapy

Advances in Precision Oncology: Targeted Thorium-227 Conjugates As a New Modality in Targeted Alpha Therapy

Hypofractionated Irradiation Suppressed the Off-Target Mouse Hepatocarcinoma Growth by Inhibiting Myeloid-Derived Suppressor Cell-Mediated Immune Suppression

A unique radioprotective effect of resolvin E1 reduces irradiation-induced damage to the inner ear by inhibiting the inflammatory response

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