Issues
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Cover Image
Cover Image
The tumor microenvironment (TME) plays a critical role in the promotion of cancer cell invasion and migration. Nerves have been shown to be a crucial component of the TME; however, the role nerve cells play in facilitating cancer cell invasion has not been fully elucidated. Deborde and colleagues demonstrated that Schwann cells (SC), the most abundant cell type in nerves, are activated by cancer cells and undergo a c-Jun–dependent reprogramming toward a nonmyelinating/repair phenotype that is characteristic of wound repair and is associated with reduced survival in patients with pancreatic cancer. Moreover, these nonmyelinating SCs form linear tracks called tumor-activated SC tracks, which serve as pathways to support and promote pancreatic cancer cell migration and invasion both in vitro and in vivo. Collectively, these findings reveal a mechanism of tumor cell invasion supported by SCs that is similar to wound repair and could potentially be targeted to prevent cancer cell invasion. For more information, see the article by Deborde and colleagues on page 2454. - PDF Icon PDF LinkTable of Contents
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In This Issue
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Research Articles
Escherichia coli–Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer
CXCL13-producing follicular helper CD4+ T cells and IgG specific to Escherichia coli are biomarkers of clinical benefit of neoadjuvant pembrolizumab in patients with muscle-invasive bladder cancer.
A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma
Intratumor myeloid inflammation independently predicts metastatic recurrence after nephrectomy in clear-cell renal cell carcinoma (ccRCC) and can be therapeutically targeted in a novel metastatic ccRCC mouse model.
Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer
Single-cell profiling of pancreatic ductal adenocarcinoma tumor-infiltrating lymphocytes provides a cell-state trajectory and indicates the GZMK+ state as an intermediate between either a GZMB+ cytotoxic state or a CXCL13+ dysfunctional state.
Geospatial Immune Heterogeneity Reflects the Diverse Tumor–Immune Interactions in Intrahepatic Cholangiocarcinoma
Multiregional immunogenomic analyses of intrahepatic cholangiocarcinoma (iCCA) demonstrate the cross-talk between tumor evolution and immune composition, providing novel insight into cancer immunoediting and personalized immunotherapy.
Modulation of BCL-2 in Both T Cells and Tumor Cells to Enhance Chimeric Antigen Receptor T-cell Immunotherapy against Cancer
Chromosomal alteration of BCL-2 leads to poorer outcomes in patients with lymphoma after anti-CD19 CART therapy, but combination of anti-CD19 CART cells overexpressing a BCL-2 mutant with venetoclax leads to synergistic antitumor effects.
The Impact of Inflammation-Induced Tumor Plasticity during Myeloid Transformation
Single-cell transcriptomic profiling of the bone marrow of a TET2-induced animal model of clonal hematopoiesis identifies inflammation as a putative driver of leukemic transformation.
A Cancer Cell–Intrinsic GOT2–PPARδ Axis Suppresses Antitumor Immunity
The mitochondrial transaminase GOT2 binds directly to fatty acid ligands that regulate the nuclear receptor PPARδ, and this functional interaction critically regulates the immune microenvironment of pancreatic cancer to promote tumor progression.
Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation
Loss-of-function alterations in LZTR1, a Cullin-3 RING E3 ubiquitin ligase adapter, and impaired ubiquitin-mediated degradation of RAS proteins via mutations in RIT1 drive clonal hematopoietic transformation.
Reprogrammed Schwann Cells Organize into Dynamic Tracks that Promote Pancreatic Cancer Invasion
Schwann cells undergo c-Jun–mediated reprogramming in pancreatic cancer, analogous to their trans-differentiation following trauma, and collectively organize into dynamic tracks that promote cancer cell invasion.
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