Canan Koksal Akbas, Federica Vurro, Claudio Fiorino, Cesare Cozzarini, Francesco Cavaliere, Paolo Milani, Sara Broggi, Antonella Del Vecchio, Nadia Di Muzio, Carlo Tacchetti, Antonello Enrico Spinelli

Preclinical photon minibeam radiotherapy using a custom collimator: Dosimetry characterization and preliminary in-vivo results on a glioma model

The purpose of this study is to investigate the dosimetric characteristics of a collimator for minibeam radiotherapy (MBRT) with film dosimetry and Monte Carlo (MC) simulations. The outcome of MBRT with respect to conventional RT using a glioma preclinical model was also evaluated.

Irma Telarovic, Carmen S. M. Yong, Lisa Kurz, Irene Vetrugno, Sabrina Reichl, Alba Sanchez Fernandez, Hung-Wei Cheng, Rona Winkler, Matthias Guckenberger, Anja Kipar, Burkhard Ludewig & Martin Pruschy

Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease

Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit.

Spencer S. Watson, Benoit Duc, Ziqi Kang, Axel de Tonnac, Nils Eling, Laure Font, Tristan Whitmarsh, Matteo Massara, iMAXT Consortium, Bernd Bodenmiller, Jean Hausser & Johanna A. Joyce

Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging

The tumor microenvironment plays a crucial role in determining response to treatment. This involves a series of interconnected changes in the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from a spatial perspective, due to the limitations of current high-dimensional imaging techniques and the extent of intratumoral heterogeneity over large lesion areas. In this study, we introduce a spatial proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes these limitations. HIFI allows for the simultaneous analysis of > 45 markers in fragile tissue sections at high magnification, using a cost-effective high-throughput workflow.

Jun Zhao, Shujun Li, Lu Xu, Chengjun Li, Qi Li, Youssef Dewer, Kongming Wu

Effects of X-Ray Irradiation on Biological Parameters and Induced Sterility of Ephestia elutella: Establishing the Optimum Irradiation Dose and Stage

The sterile insect technique (SIT) is widely used for the inundative release of sterile mass-reared males to control lepidopteran pests. SIT based on X-ray irradiation is an eco-friendly alternative to chemical control. However, its use in Ephestia elutella, a stored tobacco pest currently controlled with insecticides, is poorly explored. This study aims to investigate the effects of X-ray irradiation on E. elutella to determine the optimal sterilizing dose and processing developmental stage for improving SIT application.

Ines M Costa, George Firth, Jana Kim, Giuseppe Schettino, Gilbert O Fruhwirth, Samantha Y.A. Terry

In vitro and preclinical systematic dose-effect studies of Auger electron- and beta particle-emitting radionuclides and external beam radiation for cancer treatment

Despite a rise in clinical use of radiopharmaceutical therapies, the biological effects of radionuclides and their relationship with absorbed radiation dose are poorly understood. Here, we set out to define this relationship for Auger electron-emitters [99mTc]TcO4 and [123I]I, and β−-particle-emitter [188Re]ReO4. Studies were carried out using genetically-modified cells that permitted direct radionuclide comparisons.

Roarke A. Kamber, Yoko Nishiga, Bhek Morton, Allison M. Banuelos, Amira A. Barkal, Felipe Vences-Catalán, Mingxin Gu, Daniel Fernandez, Jose A.Seoane, David Yao, Katherine Liu, Sijie Lin, Kaitlyn Spees, Christina Curtis, Livnat Jerby-Arnon, Irving L. Weissman, Julien Sage, Michael C. Bassik

Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis

Monoclonal antibody therapies targeting tumor antigens drive cancer cell elimination in large part by triggering macrophage phagocytosis of cancer cells1–7. However, cancer cells evade phagocytosis using mechanisms that are incompletely understood. Here we develop a platform for unbiased identification of factors that impede antibody-dependent cellular phagocytosis (ADCP) using complementary genome-wide CRISPR knockout and overexpression screens in both cancer cells and macrophages. In cancer cells, beyond known factors such as CD47, we identify many regulators of susceptibility to ADCP, including the poorly characterized enzyme adipocyte plasma membrane-associated protein (APMAP).

L.M. Smith, H.E. Greenwood, W.E. Tyrrell, R.S. Edwards, V. de Santis, F. Baark, G. Firth, M. Tanc, S. Y. A. Terry, A. Herrmann, R. Southworth, T. H. Witney

The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies.

Satoshi Yamaga, Atsushi Murao, Gaifeng Ma, Max Brenner, Monowar Aziz, and Ping Wang.

Radiation upregulates macrophage TREM-1 expression to exacerbate injury in mice

Exposure to high-dose ionizing radiation causes tissue injury, infections and even death due to immune dysfunction. The triggering receptor expressed on myeloid cells-1 (TREM-1) has been demonstrated to critically amplify and dysregulate immune responses. However, the role of TREM-1 in radiation injury remains unknown. Extracellular cold-inducible RNA-binding protein (eCIRP), a new damage-associated molecular pattern, is released from activated or stressed cells during inflammation. We hypothesized that ionizing radiation upregulates TREM-1 expression via eCIRP release to worsen survival.

Laurel B. Darragh, Jacob Gadwa, Tiffany T. Pham, Benjamin Van Court, Brooke Neupert, Nicholas A. Olimpo, Khoa Nguyen, Diemmy Nguyen, Michael W. Knitz, Maureen Hoen, Sophia Corbo, Molishree Joshi, Yonghua Zhuang, Maria Amann, Xiao-Jing Wang, Steven Dow, Ross M. Kedl, Von Samedi, Mary-Keara Boss & Sana D. Karam

Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors

In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radiosensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies

I. Chiver, E. B. dos Santos, S. Valle, F. Lallemand, C. A. Cornil, G. F. Ball & J. Balthazart

Effects of the depletion of neural progenitors by focal X-ray irradiation on song production and perception in canaries

The song control nucleus HVC of songbirds has emerged as a widespread model system to study adult neurogenesis and the factors that modulate the incorporation of new neurons, including seasonal state, sex differences or sex steroid hormone concentrations. However, the specific function of these new neurons born in adulthood remains poorly understood. We implemented a new procedure based on focal X-ray irradiation to deplete neural progenitors in the ventricular zone adjacent to HVC and study the functional consequences.