Radiotherapy: killing with complement

Regal, Jean F.; Dornfeld, Kenneth J.; Fleming, Sherry D.

doi:10.21037/atm.2015.12.46

Cited by 6 publications

(3 citation statements)

References 26 publications

(20 reference statements)

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“…The activation of the complement components C3 and C5 has been known to activate and recruit neutrophils to sites of complement activation for cytotoxic killing of tumor and clearing of dead cells via phagocytosis in treatment response [84]. Generation of the cleavage product C3d following C3 activation has been associated with N1 neutrophil recruitment to damaged or stressed cells following radiotherapy, as well as in other forms of tissue injury and infection [85,86].…”

Section: Complement Activationmentioning

confidence: 99%

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

2021

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Neutrophils are the first line of defense against pathogens and abnormal cells. They regulate many biological processes such as infections and inflammation. Increasing evidence demonstrated a role for neutrophils in cancer, where different subpopulations have been found to possess both pro- or anti-tumorigenic functions in the tumor microenvironment. In this review, we discuss the phenotypic and functional diversity of neutrophils in cancer, their prognostic significance, and therapeutic relevance in human and preclinical models. Molecular imaging methods are increasingly used to probe neutrophil biology in vivo, as well as the cellular changes that occur during tumor progression and over the course of treatment. This review will discuss the role of neutrophil imaging in oncology and the lessons that can be drawn from imaging in infectious diseases and inflammatory disorders. The major factors to be considered when developing imaging techniques and biomarkers for neutrophils in cancer are reviewed. Finally, the potential clinical applications and the limitations of each method are discussed, as well as the challenges for future clinical translation.

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Section: Complement Activationmentioning

confidence: 99%

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

2021

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“…Complement is a component of the innate immune system responsible for the destruction and clearance of pathogens and damaged cells from the body, and complementmediated synaptic destruction has been implicated as a mechanism of neurodegeneration and cognitive dysfunction in aging (99) and Alzheimer's disease (100)(101)(102). While complement is known to mediate radiation-induced cell killing (103)(104)(105), to our knowledge we are the first to demonstrate that complement activation may play a role in the pathogenesis of RIBI. Additional studies are needed to verify proteolytic activation of the complement system and to identify the cellular and molecular targets of complement fixation in RIBI.…”

Section: Discussionmentioning

confidence: 96%

White Matter is the Predilection Site of Late-Delayed Radiation-Induced Brain Injury in Non-Human Primates

Andrews¹,

Dugan²,

Peiffer

et al. 2019

Radiation Research

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Fractionated whole-brain irradiation for the treatment of intracranial neoplasia causes progressive neurodegeneration and neuroinflammation. The long-term consequences of single-fraction high-dose irradiation to the brain are unknown. To assess the late effects of brain irradiation we compared transcriptomic gene expression profiles from nonhuman primates (NHP; rhesus macaques Macaca mulatta) receiving single-fraction total-body irradiation (TBI; n ¼ 5, 6.75-8.05 Gy, 6-9 years prior to necropsy) to those receiving fractionated whole-brain irradiation (fWBI; n ¼ 5, 40 Gy, 8 3 5 Gy fractions; 12 months prior to necropsy) and control comparators (n ¼ 5). Gene expression profiles from the dorsolateral prefrontal cortex (DLPFC), hippocampus (HC) and deep white matter (WM; centrum semiovale) were compared. Stratified analyses by treatment and region revealed that radiation-induced transcriptomic alterations were most prominent in animals receiving fWBI, and primarily affected white matter in both TBI and fWBI groups. Unsupervised canonical and ontologic analysis revealed that TBI or fWBI animals demonstrated shared patterns of injury, including white matter neuroinflammation, increased expression of complement factors and T-cell activation. Both irradiated groups also showed evidence of impaired glutamatergic neurotransmission and signal transduction within white matter, but not within the dorsolateral prefrontal cortex or hippocampus. Signaling pathways and structural elements involved in extracellular matrix (ECM) deposition and remodeling were noted within the white matter of animals receiving fWBI, but not of those receiving TBI. These findings indicate that those animals receiving TBI are susceptible to neurological injury similar to that observed after fWBI, and these changes persist for years postirradiation. Transcriptomic profiling reaffirmed that macrophage/ microglial-mediated neuroinflammation is present in radiation-induced brain injury (RIBI), and our data provide novel evidence that the complement system may contribute to the pathogenesis of RIBI. Finally, these data challenge the assumption that the hippocampus is the predilection site of injury in RIBI, and indicate that impaired glutamatergic neurotransmission may occur in white matter injury.

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“…Based on genomic sequencing of an individual's cancer cells, the mutations can then be targeted with compounds to block the downstream pathways that drive cancer development and progression and a more personalized treatment is achieved [62], further if combined with phenotype targeting drugs and/or immunotherapy, enormous effectiveness of cancer treatment has been observed; however the balance of risks and benefits for every combination has to be carefully evaluated in clinical trials because each therapy adds adverse effects [2] [63]. In addition, it is very worth mentioning that increasing evidence has shown that low dose radiation therapy/chemotherapy helps to break immune tolerance in patients with cancer and generate potent antitumor immune responses [64]- [67]. Thus if combination therapy is properly done, it seems likely that cures for many types of cancer will soon become reality.…”

Section: Perspectivesmentioning

confidence: 99%

Overview of Research and Development for Anticancer Drugs

Xu¹,

Mao²

2016

JCT

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Anticancer drugs research and development have been the largest market area in the pharmaceutical industry in terms of the number of project, clinical trials and spending. In the last 10 -30 years, targeting therapy for cancers has been developed and achieved enormous clinical effectiveness by transforming some previously deadly malignancies into chronically manageable conditions, but cure problem still remains. This mini review outlined the current status of anticancer drugs development and hinted the opinions of how to further increase the accuracy and efficacy of discovery for cancer treatment.

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Radiotherapy: killing with complement

Cited by 6 publications

References 26 publications

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

Clinical Translation of Neutrophil Imaging and Its Role in Cancer

White Matter is the Predilection Site of Late-Delayed Radiation-Induced Brain Injury in Non-Human Primates

Overview of Research and Development for Anticancer Drugs

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