Cytokine screening identifies TNF to potentially enhance immunogenicity of pediatric sarcomas.

Introduction: Pediatric sarcomas, including osteosarcoma (OS), Ewing sarcoma (EwS) and rhabdomyosarcoma (RMS) carry low somatic mutational burden and low MHC-I expression, posing a challenge for T cell therapies. Our previous study showed that mediators of monocyte maturation sensitized the EwS cell line A673 to lysis by HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) transgenic CD8 T cells (CHM1 CD8 T cells).

Methods: In this study, we tested a panel of monocyte maturation cytokines for their ability to upregulate immunogenic cell surface markers on OS, EwS and RMS cell lines, using flow cytometry.

Extracellular Vesicles and Their Applications in Tumor Diagnostics and Immunotherapy.

Extracellular vesicles (EVs) are cell-derived nanoparticles that have attracted significant attention in the investigation of human health and disease, including cancer biology and its clinical management. Concerning cancer, EVs have been shown to influence numerous aspects of oncogenesis, including tumor proliferation and metastasis. EVs can augment the immune system and have been implicated in virtually all aspects of innate and adaptive immunity.

Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles.

Aberrant expression of the E26 transformation-specific (ETS) transcription factors characterizes numerous human malignancies. Many of these proteins, including EWS:FLI1 and EWS:ERG fusions in Ewing sarcoma (EwS) and TMPRSS2:ERG in prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both EWS:FLI1 and ERG bind and transcriptionally activate GGAA-rich pericentromeric heterochromatin.

Hybrid Refractive-Diffractive Lens with Reduced Chromatic and Geometric Aberrations and Learned Image Reconstruction.

In this paper, we present a hybrid refractive-diffractive lens that, when paired with a deep neural network-based image reconstruction, produces high-quality, real-world images with minimal artifacts, reaching a PSNR of 28 dB on the test set. Our diffractive element compensates for the off-axis aberrations of a single refractive element and has reduced chromatic aberrations across the visible light spectrum. We also describe our training set augmentation and novel quality criteria called "false edge level" (FEL), which validates that the neural network produces visually appealing images without artifacts under a wide range of ISO and exposure settings.

Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma.

We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone.