Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

Farias, Virgínea de Araújo; Tovar, I.; Moral, R. Del; O’Valle, Francisco; Expósito, José; Oliver, F. Javier; Almodóvar, José Mariano Ruiz de

doi:10.3389/fonc.2019.01381

Cited by 23 publications

(31 citation statements)

References 152 publications

(218 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, although research on radiosensitization has made some progress, it is still in the exploratory stage. The radiotherapy resistance phenomenon of lung cancer cells still exists, which gains many uncertainties in treatment [24,25].…”

Section: Discussionmentioning

confidence: 99%

MMP10 involved in Radiosensitivity in Non-Small Cell Lung Cancer via DNA damage repair pathway

Lei

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Non-small cell lung cancer (NSCLC) is an aggressive subtype of lung cancer with high mortality and morbidity. Our purpose in this study is to investigate the effect of MMP10 in NSCLC during radiotherapy and its mechanism. Materials and methods We analyzed MMP10 expression and overall survival rate of patients via UALCAN analysis. Western blot analysis was used to test the protein expression. We applied clonogenic assay and apoptosis assay to detect radioresistance in vitro. The level of DNA damage and the DNA damage repair were disclosed via comet assay and γH2AX foci assay. Results Our results showed that high MMP10 expression in Lung Adenocarcinoma specimens is associated with poor outcomes of patients. Knockdown MMP10 induced radiosensitization in A549 cells via clonogenic assay and apoptosis assay. Furthermore, we found MMP10 siRNA enhanced DNA damage of NSCLC cells and MMP10 involved in DNA damage repair after IR. Conclusion Our data highlighted that MMP10 plays a crucial role in NSCLC after radiation via DNA damage repair pathway, and the regulating effect of MMP10 on radiosensitivity in NSCLC might confer to therapeutic implications to NSCLC radiotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

MMP10 involved in Radiosensitivity in Non-Small Cell Lung Cancer via DNA damage repair pathway

Lei

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The bioactivation of MSCs may be obtained indifferent ways [ 33 ] and the molecules secreted by the activated MSCs (MSCs*) might have an impact on several immune-cell lineages, establishing an advantageous sphere far away from its original location. We have proposed that exosomes liberated from radiation-activated MSCs* perform important intratumoral and systemic actions [ 8 , 12 ].…”

Section: Mesenchymal Stromal/stem Cells and Radiotherapymentioning

confidence: 99%

“…These results support the hypothesis that human mesenchymal stromal/stem cells are radiosensitizers for local tumor radiotherapy, and simultaneously, they represent an effective tool for amplifying the systemic effects of radiotherapy. These out-of-target radiotherapy effects [ 9 , 10 , 11 ], promoted by MSCs are, in our view, of major interest [ 9 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…We have also proved [ 7 , 8 ], that the preirradiation of MSCs triggers an important cellular change that transforms the MSCs into a source of molecules with very interesting pharmacologic proprieties. Amongst these actively secreted molecules, we have identified TRAIL and Dkk3 with very well-known antitumor activities, and annexin A1, whose activities we have previously reviewed [ 12 ] and now update here to include new data that demonstrate its anti-inflammatory and antiviral activity and its role in the regulation of hypoxia.…”

Section: Introductionmentioning

confidence: 99%

“…These effects are frequently referred to as radiation-induced out-of-target effects. Multiple molecular signaling mechanisms [ 13 ] involving oxidative stress [ 14 , 15 ], kinases, inflammatory molecules [ 16 , 17 ], exosomes [ 8 ], microvesicles are postulated to contribute to bystander short- and long-range effects [ 12 ]. The anticancer immune response may also be activated by ionizing radiation, and a combination of different treatment strategies is promising in this field [ 11 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome

Tovar

Guerrero

López-Peñalver

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients’ respiratory capacity and increase the expectations of their cure.

show abstract

An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model

Shukla

Cano‐Mejia

Andricovich

et al. 2021

Advanced NanoBiomed Research

View full text Add to dashboard Cite

A combination therapy using Prussian blue nanoparticles (PBNP) as photothermal therapy (PTT) agents coated with CpG oligodeoxynucleotides, an immunologic adjuvant, as a nanoimmunotherapy (CpG‐PBNP‐PTT) for neuroblastoma (NB) is described. NB driven by MYCN amplification confers high risk and correlates with a dismal prognosis, accounting for the majority of NB‐related mortality. The efficacy of the CpG‐PBNP‐PTT nanoimmunotherapy in a clinically relevant, TH‐MYCN murine NB model (9464D) overexpressing MYCN is tested. When administered to 9464D NB cells in vitro, CpG‐PBNP‐PTT triggers thermal dose‐dependent immunogenic cell death and tumor cell priming for immune recognition in vitro, measured by the expression of specific costimulatory and antigen‐presenting molecules. In vivo, intratumorally administered CpG‐PBNP‐PTT generates complete tumor regression and significantly higher long‐term survival compared to controls. Furthermore, CpG‐PBNP‐PTT‐treated mice reject tumor rechallenge. Ex vivo studies confirm these therapeutic responses result from the generation of robust T cell‐mediated immunological memory. Consequently, in a synchronous 9464D tumor model, CpG‐PBNP‐PTT induces complete tumor regression on the treated flank and significantly slows tumor progression on the untreated flank, improving animal survival. These findings demonstrate that localized administration of the CpG‐PBNP‐PTT nanoimmunotherapy drives potent systemic T cell responses in solid tumors such as NB and therefore has therapeutic implications for NB.

show abstract

Enhancing the Bystander and Abscopal Effects to Improve Radiotherapy Outcomes

Cited by 23 publications

References 152 publications

MMP10 involved in Radiosensitivity in Non-Small Cell Lung Cancer via DNA damage repair pathway

MMP10 involved in Radiosensitivity in Non-Small Cell Lung Cancer via DNA damage repair pathway

Rationale for the Use of Radiation-Activated Mesenchymal Stromal/Stem Cells in Acute Respiratory Distress Syndrome

An Engineered Prussian Blue Nanoparticles‐Based Nanoimmunotherapy Elicits Robust and Persistent Immunological Memory in a TH‐MYCN Neuroblastoma Model

Contact Info

Product

Resources

About