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Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.

ABSTRACT: While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays. We compared the potential of photon and carbon ion radiation to induce cell cycle arrest, altered surface expression of immunomodulatory molecules and changes in the susceptibility of cancer cells to cytotoxic T cell (CTL) mediated killing. Irradiation induced a dose-dependent G2/M arrest in both cell lines irrespective from the irradiation source applied. Likewise, surface expression of the immunomodulatory molecules PD-L1, CD73, H2-D^b and H2-K^b was increased in a dose-dependent manner. Both radiation modalities enhanced the susceptibility of tumor cells to CTL lysis, which was more pronounced in EO771/Luci/OVA cells than in PDA30364/OVA cells. Overall, compared to photon radiation, the effects of carbon ion radiation appeared to be enhanced at higher dose range for EO771 cells and extenuated at lower dose range for PDA30364/OVA cells. Our data show for the first time that equivalent doses of carbon ion and photon irradiation exert similar immunomodulating effects on the cell lines of both tumor entities, highlighted by an enhanced susceptibility to CTL mediated cytolysis in vitro.

SUBMITTER: Hartmann L

PROVIDER: S-EPMC7726046 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.

Hartmann Laura L Schröter Philipp P Osen Wolfram W Baumann Daniel D Offringa Rienk R Moustafa Mahmoud M Will Rainer R Debus Jürgen J Brons Stephan S Rieken Stefan S Eichmüller Stefan B SB

Scientific reports 20201209 1

While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO ...[more]

PMID: 33299018

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Project description:Purpose: To perform a prospective study to evaluate the efficacy and safety of isolated recurrent tumor re-irradiation with carbon-ion radiotherapy (RT). Methods and Materials: The inclusion criteria were clinically proven recurrent tumors, measurable by computed tomography or magnetic resonance imaging, patients ≥ 16 years old, performance status scores between 0 and 2, isolated tumor at a previously irradiated site, and a life expectancy > 6 months. The exclusion criteria were tumor invasion into the gastrointestinal tract or a major blood vessel, uncontrolled infection, early recurrence (<3 months), and severe concomitant diseases. The primary end-point was the local control rate, the secondary end-points including the overall survival rate, and adverse events. Results: Between December 2013 and March 2016, 22 patients were enrolled in this prospective study. All patients were re-irradiated with carbon-ion RT with radical intent. Five patients had rectal cancer, 4 had sarcoma, 4 had lung cancer, 3 had hepatic cell carcinoma, and 6 had other tumors. The median follow-up time was 26 months. Eight patients developed local recurrence, and the 1- and 2-year local control rates were 71 and 60%, respectively. Eight patients died of their cancers and 2 died of other diseases. The 1- and 2-year overall survival rates were 76 and 67%, respectively. There were no grade 2 or higher acute adverse events and 4 patients (18%) developed grade 3 late adverse events. The group with the longer interval (>16 months) between the first RT and re-irradiation had significantly better outcomes than the shorter interval group (≤ 16 months). Conclusions: Re-irradiation, using carbon-ion RT with radical intent, had favorable local control and overall survival rates without severe toxicities for selected patients. Re-irradiation has the potential to improve clinical outcomes for isolated, local, recurrent tumors; further investigations are required to confirm the therapeutic efficacy.

Project description:BackgroundIn this study, we assessed the actively metabolizing bacteria in the rhizosphere of potato using two potato cultivars, i.e. the genetically-modified (GM) cultivar Modena (having tubers with altered starch content) and the near-isogenic non-GM cultivar Karnico. To achieve our aims, we pulse-labelled plants at EC90 stage with (13)C-CO2 and analysed their rhizosphere microbial communities 24 h, 5 and 12 days following the pulse. In the analyses, phospholipid fatty acid/stable isotope probing (PLFA-SIP) as well as RNA-SIP followed by reverse transcription and PCR-DGGE and clone library analysis, were used to determine the bacterial groups that actively respond to the root-released (13)C labelled carbonaceous compounds.Methodology/principal findingsThe PLFA-SIP data revealed major roles of bacteria in the uptake of root-released (13)C carbon, which grossly increased with time. Gram-negative bacteria, including members of the genera Pseudomonas and Burkholderia, were strong accumulators of the (13)C-labeled compounds at the two cultivars, whereas Gram-positive bacteria were lesser responders. PCR-DGGE analysis of cDNA produced from the two cultivar types showed that these had selected different bacterial, alpha- and betaproteobacterial communities at all time points. Moreover, an effect of time was observed, indicating dynamism in the structure of the active bacterial communities. PCR-DGGE as well as clone library analyses revealed that the main bacterial responders at cultivar Karnico were taxonomically affiliated with the genus Pseudomonas, next to Gluconacetobacter and Paracoccus. Cultivar Modena mainly attracted Burkholderia, next to Moraxella-like (Moraxellaceae family) and Sphingomonas types.Conclusions/significanceBased on the use of Pseudomonas and Burkholderia as proxies for differentially-selected bacterial genera, we conclude that the selective forces exerted by potato cultivar Modena on the active bacterial populations differed from those exerted by cultivar Karnico.

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Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.

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Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.

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