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Article
Differential expression of small bowel TGFβ1 and TGFβ3 characterizes intestinal strictures in patients with fibrostenotic Crohn’s disease
Small bowel strictures remain a debilitating consequence of Crohn’s disease and contribute to poor outcomes for patients. Recently, TGFβ has been identified as an important driver of intestinal fibrosis. We st...
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Article
Open AccessTumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer
Microsatellite-stable colorectal cancer (MSS-CRC) is highly refractory to immunotherapy. Understanding tumor-intrinsic determinants of immunotherapy resistance is critical to improve MSS-CRC patient outcomes. ...
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Article
Open AccessCombined PD-L1/TGFβ blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors
TGFβ signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. While previous work demonstrates that converting t...
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Article
Correction to: Preclinical development of ZED8, an 89Zr immuno‑PET reagent for monitoring tumor CD8 status in patients undergoing cancer immunotherapy
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Protocol
Mass Spectrometry-Based Tissue Imaging of the Tumor Microenvironment
Multiplex ion beam imaging (MIBI) and imaging mass cytometry (IMC) enable highly multiplexed antibody (40+) staining of frozen or formalin fixed, paraffin-embedded (FFPE) human or murine tissues through detect...
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Article
Preclinical development of ZED8, an 89Zr immuno-PET reagent for monitoring tumor CD8 status in patients undergoing cancer immunotherapy
ZED8 is a novel monovalent antibody labeled with zirconium-89 for the molecular imaging of CD8. This work describes nonclinical studies performed in part to provide rationale for and to inform expectations in ...
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Article
Open AccessLRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity
Recent single-cell studies of cancer in both mice and humans have identified the emergence of a myofibroblast population specifically marked by the highly restricted leucine-rich-repeat-containing protein 15 (...
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Article
Loss of the intracellular enzyme QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity
Tumor-associated macrophages are composed of distinct populations arising from monocytes or tissue macrophages, with a poorly understood link to disease pathogenesis. Here, we demonstrate that mouse monocyte m...
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Article
Open AccessIntegrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer
Close proximity between cytotoxic T lymphocytes and tumour cells is required for effective immunotherapy. However, what controls the spatial distribution of T cells in the tumour microenvironment is not well u...
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Article
Open AccessThe Indian cobra reference genome and transcriptome enables comprehensive identification of venom toxins
Snakebite envenoming is a serious and neglected tropical disease that kills ~100,000 people annually. High-quality, genome-enabled comprehensive characterization of toxin genes will facilitate development of e...
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Article
Open AccessS100a4 upregulation in Pik3caH1047R;Trp53R270H;MMTV-Cre-driven mammary tumors promotes metastasis
PIK3CA mutations are frequent in human breast cancer. Pik3caH1047R mutant expression in mouse mammary gland promotes tumorigenesis. TP53 mutations co-occur with PIK3CA mutations in human breast cancers. We previo...
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Article
Inhibition of the dipeptidyl peptidase DPP4 (CD26) reveals IL-33-dependent eosinophil-mediated control of tumor growth
Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tum...
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Article
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression...
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Article
Open AccessAtezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma
Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclin...
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Article
Open AccessHeterogeneity of cytotoxic T cell infiltration in breast and colorectal cancer
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Article
Open AccessPrevalence analysis of OX40-positive cell populations in solid tumors
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Article
Open AccessA CD4/Foxp3/OX40 triple immunofluorescence assay determines association between T cell immune subsets and outcome in colorectal cancer
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Article
NUT Gene Rearrangement in a Poorly-differentiated Carcinoma of the Submandibular Gland
NUT midline carcinomas (NMC) are a rare, recently described class of poorly-differentiated tumors that exhibit rapid onset and highly aggressive clinicopathologic behavior. These tumors are defined by rearrang...