IDO1 + Paneth cells promote immune escape of colorectal cancer

Abstract: Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy

IDO1 + Paneth cells promote immune escape of colorectal cancer

Abstract: Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy

On-line 3D motion estimation using low resolution MRI

Image processing such as deformable image registration finds its way into radiotherapy as a means to track non-rigid anatomy. With the advent of magnetic resonance imaging ( MRI ) guided radiotherapy, intrafraction anatomy snapshots become technically feasible.magnetic resonance ( MR ) imaging provides the needed tissue signal for high-fidelity image registration. However, acquisitions, especially in 3D, take a considerable amount of time. Pushing towards real-time adaptive radiotherapy, MR imaging needs to be accelerated without degrading the quality of information.In this paper, we investigate the impact of image resolution on the quality of motion estimations. Potentially, spatially undersampled images yield comparable motion estimations. At the same time, their acquisition times would reduce greatly due to the sparser sampling. In order to substantiate this hypothesis, an exemplary 4D dataset of the abdomen is downsampled gradually. Subsequently, spatiotemporal deformations are extracted consistently using the same motion estimation for each downsampled dataset. Errors between the original and the respectively downsampled version are then evaluated.Compared to ground-truth, results show high similarity of deformations estimated from downsampled image data. Using a dataset with (2.5mm) 3 voxel size, deformation fields could be recovered well up to a downsampling factor of 2, i.e. (5mm) 3 . In a therapy guidance scenario MRI , imaging speed would accordingly increase approximately fourfold, with acceptable loss of estimated motion quality

MRI B 0 homogeneity and geometric distortion with continuous linac gantry rotation on an Elekta Unity MR-linac

This work aimed to quantify any principal magnetic field (B 0) inhomogeneity and changes in MR image geometric distortion with continuous linac gantry rotation on an Elekta Unity MR-linac. This situation occurs for around a second between treatment beams during current image guided radiotherapy treatment and would occur frequently in foreseeable real-time adaptive radiotherapy treatment. Pixel by pixel maps of B 0 inhomogeneity were obtained via repeated high temporal resolution pulse sequences with the linac gantry static at 36 gantry angles spaced ten degrees apart, and in continuous rotation at both 1 and 2 rpm. Individual B 0 maps were subtracted from average maps across all data and the residual peak to peak inhomogeneity was calculated for each. The bulk geometric shift and change in physical extent of a 10 cm diameter spherical flood phantom during continuous linac gantry rotation at 1 and 2 rpm was compared to the static gantry case for two pulse sequences: the real-time clinical monitoring bFFE sequence and a non-clinical EPI sequence, chosen for its susceptibility to geometric distortion. The peak to peak inhomogeneity in the deviation-from-average ppm maps, plotted against gantry angle with the gantry in continuous rotation at 1 and 2 rpm were negligibly different from equivalent data obtained with the gantry static. The real-time clinical monitoring pulse sequence was shown to give negligible geometric distortion during continuous gantry motion, whilst a non-clinical EPI sequence showed bulk shifts of the order of one pixel and gantry angle dependent changes in extent, demonstrating the sensitivity of the chosen method. MR imaging on the Elekta Unity MR-Linac with the gantry in continuous motion is negligibly different from the static gantry case with current clinical pulse sequences. Real-time tracking and treatment plan adaptation using MR images obtained with the linac gantry in motion is possible

MRI B 0 homogeneity and geometric distortion with continuous linac gantry rotation on an Elekta Unity MR-linac

This work aimed to quantify any principal magnetic field (B 0) inhomogeneity and changes in MR image geometric distortion with continuous linac gantry rotation on an Elekta Unity MR-linac. This situation occurs for around a second between treatment beams during current image guided radiotherapy treatment and would occur frequently in foreseeable real-time adaptive radiotherapy treatment. Pixel by pixel maps of B 0 inhomogeneity were obtained via repeated high temporal resolution pulse sequences with the linac gantry static at 36 gantry angles spaced ten degrees apart, and in continuous rotation at both 1 and 2 rpm. Individual B 0 maps were subtracted from average maps across all data and the residual peak to peak inhomogeneity was calculated for each. The bulk geometric shift and change in physical extent of a 10 cm diameter spherical flood phantom during continuous linac gantry rotation at 1 and 2 rpm was compared to the static gantry case for two pulse sequences: the real-time clinical monitoring bFFE sequence and a non-clinical EPI sequence, chosen for its susceptibility to geometric distortion. The peak to peak inhomogeneity in the deviation-from-average ppm maps, plotted against gantry angle with the gantry in continuous rotation at 1 and 2 rpm were negligibly different from equivalent data obtained with the gantry static. The real-time clinical monitoring pulse sequence was shown to give negligible geometric distortion during continuous gantry motion, whilst a non-clinical EPI sequence showed bulk shifts of the order of one pixel and gantry angle dependent changes in extent, demonstrating the sensitivity of the chosen method. MR imaging on the Elekta Unity MR-Linac with the gantry in continuous motion is negligibly different from the static gantry case with current clinical pulse sequences. Real-time tracking and treatment plan adaptation using MR images obtained with the linac gantry in motion is possible

On-line MR imaging for dose validation of abdominal radiotherapy

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial.Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dosecalculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant. In particular, hypofractionated and escalated radiotherapy thus demand for reliable dose reconstruction based on periodic imaging.In this paper, we investigate the use of an MR -linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occurs.The on-line MR imaging capabilities of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions.In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planing grid to obtain the actual dose accumulated over the entire treatment duration. Eventually, the planned dose was validated by comparison with the accumulated dose.Representatively for a site subject to breathing modulation, two kidney cases (25Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations −2.3 to 1.5Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from −2.5 to 1.9Gy could be traced back

Real-time auto-adaptive margin generation for MLC-tracked radiotherapy

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MRI commissioning of 1.5T MR-linac systems – a multi-institutional study

Background: Magnetic Resonance linear accelerator (MR-linac) systems represent a new type of technology that allows for online MR-guidance for high precision radiotherapy (RT). Currently, the first MR-linac installations are being introduced clinically. Since the imaging performance of these integrated MR-linac systems is critical for their application, a thorough commissioning of the MRI performance is essential. However, guidelines on the commissioning of MR-guided RT systems are not yet defined and data on the performance of MR-linacs are not yet available. Materials & methods: Here we describe a comprehensive commissioning protocol, which contains standard MRI performance measurements as well as dedicated hybrid tests that specifically assess the interactions between the Linac and the MRI system. The commissioning results of four MR-linac systems are presented in a multi-center study. Results: Although the four systems showed similar performance in all the standard MRI performance tests, some differences were observed relating to the hybrid character of the systems. Field homogeneity measurements identified differences in the gantry shim configuration, which was later confirmed by the vendor. Conclusion: Our results highlight the importance of dedicated hybrid commissioning tests and the ability to compare the machines between institutes at this very early stage of clinical introduction. Until formal guidelines and tolerances are defined the tests described in this study may be used as a practical guideline. Moreover, the multi-center results provide initial bench mark data for future MR-linac installations

Effect of intra-fraction motion on the accumulated dose for free-breathing MR-guided stereotactic body radiation therapy of renal-cell carcinoma

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