5,576 research outputs found
Abstract PL1: Potential of Radiation Therapy to Convert the Tumor Into an In Situ Vaccine
No full textAbstract
Radiotherapy (RT) has revealed an ideal adjuvant to cancer immunotherapy, because of it's ability to convert the irradiated tumor into an individualized, in situ vaccine. 1 DNA damage response (DDR) contributes to immune rejection of tumors, a mechanism at least in part responsible of the success of platinum and RT combinations. 2 RT-induced cell death can evoke T cell memory, inducing effects outside the irradiated field, defined as abscopal. In the setting of metastatic cancer, however, the occurrence of abscopal effects is extremely rare, 3 because of the established immune-suppressive microenvironment. 4 Thus, the pro-immunogenic effects of radiotherapy is best exploited in combination with immunotherapy, 5,6 and combination of RT and immune checkpoint blockade (ICB) has matured to reach clinical translation. 7 8
The issue of RT dose and fractionation is particularly relevant to abscopal responses. 8,9 A mechanism underlying this dose-dependence was recently elucidated. 10 In mice bearing bilateral TSA murine breast carcinoma a single dose of 20 or 30Gy combined with ICB achieved comparable in field control to that of a regimen of 8GyX3 fractions, but only the fractionated regimen induced abscopal responses. An interferon type I (IFN-I) gene signature was associated with the 8GyX3 fractions but not with a single dose of 20 or 30 Gy. IFN-I plays a key role in cross priming and rejection of cancer. 11 RT-generates double strands (ds) DNA fragments reach the cytoplasm of irradiated cells where they are “sensed” by cGAS/STING (cGAS=cyclic GMP-AMP synthase and its adaptor protein STING= stimulator of interferon genes, aka transmembrane protein 173 – TMEM173). cGAS binds cytosolic dsDNA to initiate IFN-I responses upon STING stimulation, resulting in dendritic cell recruitment and cross-priming of effector T-cells, key steps to convert the tumor into an in situ vaccine. In multiple carcinoma murine and human carcinoma cells as the radiation dose increased, cytosolic dsDNA was found to accumulate to a threshold above which induction of three prime repair exonuclease 1 (Trex1) occured, an enzyme that degrades cytoplasmic DNA. Single doses in excess of 10-12 Gy induced Trex1, with rapid degradation of cytosolic dsDNA, and abrogation of IFN induction, impairing RT-induced abscopal effects. These findings support the choice of 3-5 doses of 8 Gy each, when radiotherapy is combined with immunotherapy. Interestingly, a recent dose escalation clinical trial demonstrated an inferior incidence of pathological response (pCR) when breast cancers were irradiated beyond a certain threshold: pCR was 67% in the cohort treated with 8.5 Gy X3 and decreased to 43 and 33% after three fractions of 9.5Gy and 10.5 Gy, respectively. 12 Ongoing investigations are defining optimal sequencing and treatment fields.
1. OncoImmunology 2014; 3: e28518.
2. Oncoimmunology 2017; 6(3): e1274479.
3. Curr Probl Cancer 2016; 40: 25-37.
4. Annu Rev Immunol 2011; 29: 235-71.
5. Int J Radiat Oncol Biol Phys 2004; 58: 862-70.
6. Lancet Oncol 2015; 16(7): 795-803.
7. Clin Cancer Res 2005; 11: 728-34.
8. J Immunother Cancer 2016; 4: 51.
9. Clin Cancer Res 2009; 15(17): 5379-88.
10. Nat Commun 2017; 8: 15618.
11.Trends Immunol 2013; 34(2): 67-73.
12. Int J Radiat Oncol Biol Phys 2013; 85(5): 1193-9.
Citation Format: Formenti SC. Potential of Radiation Therapy to Convert the Tumor Into an In Situ Vaccine [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PL1.</jats:p
SC author and illustrator Kate Salley Palmer signing book
No full textPhotograph of SC author and illustrator Kate Salley Palmer signing boo
Book signing by SC author and illustrator Kate Salley Palmer
No full textPhotograph of Book signing by SC author and illustrator Kate Salley Palme
High-resolution clean-sc
No full textIn this paper a high-resolution extension of CLEAN-SC is proposed: HR-CLEAN-SC. Where CLEAN-SC uses peak sources in “dirty maps” to define so-called source components, HR-CLEAN-SC takes advantage of the fact that source components can likewise be derived from points at some distance from the peak, as long as these “source markers” are on the main lobe of the Point Spread Function (PSF). This is very useful when sources are closely spaced together, such that their PSFs interfere. Then, alternative markers can be sought in which the relative influence by PSFs of other source positions is minimised. For those markers the source components better agree with the actual sources, which allows for better estimation of their locations and strengths. This paper outlines the theory needed to understand this approach and discusses applications to 2D and 3D microphone array simulations with closely spaced sources
SC author and illustrator Kate Salley Palmer talking to event attendees
No full textPhotograph of SC author and illustrator Kate Salley Palmer talking to Rita Lewi
Ca-modified Al–Mg–Sc alloy with high strength at elevated temperatures due to a hierarchical microstructure
No full textAl-Mg alloys are normally prone to lose part of their yield and tensile strength at high temperatures due to insufficient thermal stability of the microstructure. Here, we present a Ca-modified Al–Mg–Sc alloy demonstrating high strength at elevated temperatures. The microstructure contains Al4Ca phases distributed as a network along the grain boundary and Al3(Sc,Zr) nano-particles dispersed within the grains. The microstructure evolution and age-hardening analysis indicate that the combination of an Al4Ca network and Sc-rich nano-particles leads to excellent thermal stability even upon aging at 300 °C. The tensile strength of the alloy for temperatures up to 250 °C is significantly improved by an aging treatment and is comparable with the commercial heat-resistant aluminum alloys, i.e., A356 and A319. At a high temperature of 300 °C, the tensile strength is superior to the above-mentioned commercial alloys, even more so when expressed as the specific strength due to the low density of Ca-modified Al–Mg–Sc alloy. The excellent high-temperature strength results from a synergistic effect of solid solution strengthening, grain boundary strengthening and nanoparticle order strengthening.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Novel Aerospace Material
SC-Square: Overview to 2021.
No full textThis extended abstract was written to accompany an invited talk at the 2021 SC-Square Workshop, where the author was asked to give an overview of SC-Square progress to date. The author first reminds the reader of the definition of SC-Square, then briefly outlines some of the history, before picking out some (personal) scientific highlights
SC-Square: Overview to 2021.
No full textThis extended abstract was written to accompany an invited talk at the 2021 SC-Square Workshop, where the author was asked to give an overview of SC-Square progress to date. The author first reminds the reader of the definition of SC-Square, then briefly outlines some of the history, before picking out some (personal) scientific highlights
Supply Chain (SC) Network Optimization
No full textSupply chain network design and optimization is one of the most important strategic decisions that an organization has to make. SC network design decisions are strategic-level SC decisions because they have long-lasting effect on the firms' supply chain performance and the decisions cannot be changed in a short period. In this chapter, the author aims to introduce the concept of SC network optimization to the managers of medium-sized enterprises. The chapter also explains the importance of the SC network optimization studies, educates readers about how they can benefit from the concept, and tries to show how the implementation of SC network optimization/design will improve the competitiveness of these organizations. The readers are also guided through the four steps of SC network optimization process. Finally, the chapter provides a brief review of the SC network optimization literature and proposes future research directions. </jats:p
The turbulence structure of 3D separation (Stall Cells) over an airfoil
No full textThe flow over airfoils that experience separation of the trailing edge type becomes three-dimensional at angles of attack around maximum lift and Stall Cells (SCs) form. SCs are large scale coherent structures of separated flow that consist of two counter-rotating vortices. In the present study the turbulence structure of a SC over a rectangular wing is investigated using Stereo PIV measurements. It is found that the turbulence characteristics of the flow are highly anisotropic and that the Boussinesq approximation is invalid. High values of normal Reynolds stresses in the SC vortices and the separation shear layer region indicates a wandering motion of the former and a flapping motion of the latter. Based on the available data the relation between Reynolds stresses, their production terms and the mean flow gradients is examined. It is found that at the centre of the SC, between the two vortices, the flow characteristics resemble those of a double shear layer while at the vortex region the effect of the vortices leads to double peaks in production terms
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