Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation.

Background: While major advances have been made in improving the quality of life and survival of children with most forms of medulloblastoma (MB), those with MYC-driven tumors (Grp3-MB) still suffer significant morbidity and mortality. There is an urgent need to explore multimodal therapeutic regimens which are effective and safe for children. Large-scale studies have revealed abnormal cancer epigenomes caused by mutations and structural alterations of chromatin modifiers, aberrant DNA methylation, and histone modification signatures.

Impact of timing and precision of histopathological diagnosis on outcomes of patients with Burkitt lymphoma and high-grade B-cell lymphoma.

Background: Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are aggressive B-cell non-Hodgkin lymphomas (B-NHL) with a generally favorable prognosis after immunochemotherapy. The outcome of BL is superior to DLBCL. In 2016, a distinct group of lymphomas displaying characteristics of both BL and DLBCL (high grade B-cell lymphoma, HGBL) was introduced into the WHO classification.

Intercellular cGAMP transmission induces innate immune activation and tissue inflammation in Trex1 deficiency.

Intercellular transmission of the second messenger 2',3'-cGAMP, synthesized by the viral DNA sensor cGAMP synthase (cGAS), is a potent mode of bystander activation during host defense. However, whether this mechanism also contributes to cGAS-dependent autoimmunity remains unknown. Here, using a murine bone marrow transplantation strategy, we demonstrate that, in -associated autoimmunity, cGAMP shuttling from radioresistant to immune cells induces NF-κB activation, interferon regulatory factor 3 (IRF3) phosphorylation, and subsequent interferon signaling.

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors.

Atypical teratoid/rhabdoid tumors (ATRTs) typically arise in the central nervous system (CNS) of children under 3 years of age. Despite intensive multimodal therapy (surgery, chemotherapy and, if age permits, radiotherapy), median survival is 17 months. We show that ATRTs robustly express B7-H3/CD276 that does not result from the inactivating mutations in SMARCB1 (refs.

Spatiotemporal Tracking of Brain-Tumor-Associated Myeloid Cells through Optical Coherence Tomography with Plasmonic Labeling and Speckle Modulation.

By their nature, tumors pose a set of profound challenges to the immune system with respect to cellular recognition and response coordination. Recent research indicates that leukocyte subpopulations, especially tumor-associated macrophages (TAMs), can exert substantial influence on the efficacy of various cancer immunotherapy treatment strategies. To better study and understand the roles of TAMs in determining immunotherapeutic outcomes, significant technical challenges associated with dynamically monitoring single cells of interest in relevant live animal models of solid tumors must be overcome.

Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma.

CD47 monoclonal antibodies (mAbs) activate tumor-associated macrophages (TAMs) in sarcomas to phagocytose and eliminate cancer cells. Though CD47 mAbs have entered clinical trials, diagnostic tests for monitoring therapy response in vivo are currently lacking. Ferumoxytol is an FDA-approved iron supplement which can be used "off label" as a contrast agent: the nanoparticle-based drug is phagocytosed by TAM and can be detected with magnetic resonance imaging (MRI).

Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma.

Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with fatal outcome. Tumor-associated macrophages and microglia (TAMs) have been found to be major tumor-promoting immune cells in the tumor microenvironment. Hence, modulation and reeducation of tumor-associated macrophages and microglia in GBM is considered a promising antitumor strategy.