Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding.

Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis.

Age-Dependent Bi-Phasic Dynamics of Ly49CD8 Regulatory T Cell Population.

Aging is tightly associated with reduced immune protection but increased risk of autoimmunity and inflammatory conditions. Regulatory T cells are one of the key cells to maintaining immune homeostasis. The age-dependent changes in CD4Foxp3 regulatory T cells (Tregs) have been well documented.

The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation.

During persistent antigen stimulation, exhausted CD8 T cells are continuously replenished by self-renewing stem-like T cells. However, how CD8 T cells adapt to chronic stimulation remains unclear. Here, we show that persistent antigen stimulation primes chromatin for regulation by the redox-sensing KEAP1-NRF2 pathway.

Direct activation of toll-like receptor 4 signaling in group 2 innate lymphoid cells contributes to inflammatory responses of allergic diseases.

Group 2 innate lymphoid cells (ILC2s) are key players in type 2 immunity, but whether they can be directly activated by microbial ligands remain uncertain. In this study, we observed a positive correlation between blood endotoxin (LPS) levels and circulating ILC2s in allergic patients. , LPS robustly induced ILC2 proliferation and production of type 2 effector cytokines.

Corrigendum: Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes.

[This corrects the article DOI: 10.3389/fimmu.2024.

The Laws of Attraction: Chemokines as Critical Mediators in Cancer Progression and Immunotherapy Response in Bladder Cancer.

Bladder cancer (BCa) is a prevalent urogenital malignancy, characterized by a myriad of genetic and environmental risk factors that drive its progression. Approximately 75% of bladder tumors are non-muscle-invasive at diagnosis. For such cases, bladder preservation is often feasible with intravesical chemotherapy or immunotherapy.

A peptide encoded by upstream open reading frame of binds to tropomyosin receptor kinase B and promotes glioblastoma growth in mice.

MYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) . Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling.

Dynamic structural remodeling of LINC01956 enhances temozolomide resistance in -methylated glioblastoma.

The mechanisms underlying stimuli-induced dynamic structural remodeling of RNAs for the maintenance of cellular physiological function and survival remain unclear. Here, we showed that in promoter-methylated glioblastoma (GBM), the RNA helicase DEAD-box helicase 46 (DDX46) is phosphorylated by temozolomide (TMZ)-activated checkpoint kinase 1 (CHK1), resulting in a dense-to-loose conformational change and an increase in DDX46 helicase activity. DDX46-mediated tertiary structural remodeling of LINC01956 exposes the binding motifs of LINC01956 to the 3' untranslated region of O-methylguanine DNA methyltransferase ().

Into the storm: the imbalance in the yin-yang immune response as the commonality of cytokine storm syndromes.

There is a continuous cycle of activation and contraction in the immune response against pathogens and other threats to human health in life. This intrinsic yin-yang of the immune response ensures that inflammatory processes can be appropriately controlled once that threat has been resolved, preventing unnecessary tissue and organ damage. Various factors may contribute to a state of perpetual immune activation, leading to a failure to undergo immune contraction and development of cytokine storm syndromes.

Tenovin-6 exhibits inhibitory effects on the growth of Sonic Hedgehog (SHH) medulloblastoma, as evidenced by both in vitro and in vivo studies.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Within MB, tumors driven by the Sonic Hedgehog (SHH) pathway represent the most heterogeneous subtype, known as SHH subtype medulloblastoma (SHH-MB). Tenovin-6, a recognized p53 activator, has been demonstrated to inhibit autophagy and modulate sirtuin activity, underscoring its potential as a novel therapeutic agent across various malignancies.

Epithelial organoid supports resident memory CD8 T cell differentiation.

Resident memory T cells (TRMs) play a vital role in regional immune defense. Although laboratory rodents have been extensively used to study fundamental TRM biology, poor isolation efficiency and low cell survival rates have limited the implementation of TRM-focused high-throughput assays. Here, we engineer a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system that supports CD8 TRM differentiation.

Heterogeneous stiffness of the bone marrow microenvironment regulates the fate decision of haematopoietic stem and progenitor cells.

The bone marrow (BM) niches are the complex microenvironments that surround cells, providing various external stimuli to regulate a range of haematopoietic stem cell (HSC) behaviours. Recently, it has been proposed that the fate decision of HSCs is often correlated with significantly altered biophysical signals of BM niches. To thoroughly elucidate the effect of mechanical microenvironments on cell fates, we constructed 2D and 3D cell culture hydrogels using polyacrylamide to replicate the mechanical properties of heterogeneous sub-niches, including the inherent rigidity of marrow adipose tissue (2 kPa), perivascular tissue (8 kPa) and endosteum region (35 kPa) in BM.

Antibody-activation of connexin hemichannels in bone osteocytes with ATP release suppresses breast cancer and osteosarcoma malignancy.

Bone tissue represents the most frequent site of cancer metastasis. We developed a hemichannel-activating antibody, Cx43-M2. Cx43-M2, directly targeting osteocytes in situ, activates osteocytic hemichannels and elevates extracellular ATP, thereby inhibiting the growth and migration of cultured breast and osteosarcoma cancer cells.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers.

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM.

T-bet deficiency and Hic1 induction override TGF-β-dependency in the formation of CD103 intestine-resident memory CD8 T cells.

Transforming growth factor β (TGF-β) represents a well-established signal required for tissue-resident memory T cell (T) formation at intestinal surfaces, regulating the expression of a large collection of genes coordinately promoting intestinal T differentiation. The functional contribution from each TGF-β-controlled transcription factor is not entirely known. Here, we find that TGF-β-induced T-bet downregulation and Hic1 induction represent two critical events during intestinal T differentiation.

SARS-CoV-2 Omicron Variants Show Attenuated Neurovirulence Compared with the Wild-Type Strain in Elderly Human Brain Spheroids.

Infection with severe acute respiratory syndrome coronavirus 2 Omicron variants still causes neurological complications in elderly individuals. However, whether and how aging brains are affected by Omicron variants in terms of neuroinvasiveness and neurovirulence are unknown. Here, we utilize resected paracarcinoma brain tissue from elderly individuals to generate primary brain spheroids (BSs) for investigating the replication capability of live wild-type (WT) strain and Omicron (BA.

IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME.

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

Purpose: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function.

Methods: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST.

Epithelial organoid supports resident memory CD8 T cell differentiation.

Resident Memory T cells (TRM) play a vital role in regional immune defense in barrier organs. Although laboratory rodents have been extensively used to study fundamental TRM biology, poor isolation efficiency, sampling bias and low cell survival rates have limited our ability to conduct TRM-focused high-throughput assays. Here, we engineered a murine vaginal epithelial organoid (VEO)-CD8 T cell co-culture system that supports CD8 TRM differentiation .

Choroid plexus mast cells drive tumor-associated hydrocephalus.

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH.