Cancer

Abstract CT204: A phase 1, first in human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors

Background: Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but not in those with solid tumors. Macrophages are actively recruited into, and abundantly present in the solid tumor microenvironment (sTME). Tumor- associated macrophages typically evince immunosuppressive behavior, but when engineered to be proinflammatory, may be an ideal vector to administer adoptive cellular therapy in solid tumors.

Abstract LB235: Characterizing tumor-infiltrated immune cells with spatial context using an integrated RNAscope-immunohistochemistry co-detection workflow in FFPE tissues

Complex tissues such as tumors are comprised of multiple cells types and extracellular matrix. These cells include heterogenous populations of immune cells that infiltrate the tumors. Understanding the composition of these immune infiltrates in the tumor microenvironment (TME) can provide key insights to guide therapeutic intervention and predict treatment response. Thorough understanding of complex tissue dynamics and immune cell characterization requires a multi-omics approach.

First-in-human DR5 PET reveals insufficient DR5 expression in patients with gastrointestinal cancer

Death receptor 5 (DR5) is a promising therapeutic target for cancer therapy. However, many clinical trials of DR5 agonists failed to show significant therapeutic efficacy in patients with cancer. The study aimed to investigate the feasibility of using 89Zr-CTB006 positron emission tomography (PET) for noninvasive imaging of DR5 expression in preclinical models and patients with gastrointestinal (GI) cancers.Balb/c, Sp2/0 xenograft and patient-derived tumor xenograft were employed for micro-PET/CT imaging in vivo.

A live single-cell reporter assay links intratumor heterogeneity to metastatic proclivity in Ewing sarcoma

Targeting of the most aggressive tumor cell subpopulations is key for effective management of most solid malignancies. However, the metastable nature of tumor heterogeneity, which allows cells to transition between strong and weak tumorigenic phenotypes, and the lack of reliable markers of tumor-promoting properties hamper identification of the most relevant cells. To overcome these obstacles, we designed a functional microRNA (miR)-based live-cell reporter assay to identify highly tumorigenic cells in xenotransplants of primary Ewing sarcoma (EwS) 3D cultures.

IN SITU DETECTION OF CRTC-MAML2 TRANSLOCATION EXPRESSION IN MUCOEPIDERMOID CARCINOMA

Background The heterogeneity of salivary gland neoplasms, within and between histologic types, presents a major diagnostic challenge. Mucoepidermoid carcinoma (MEC), the most common salivary gland cancer in adults, children, and adolescents, is associated with the presence of a novel CRTC1-MAML2 fusion gene. The translocation can be detected by fluorescence in situ hybridization or reverse transcription polymerase chain reaction but without information regarding transcript level, identification of the cell type(s) harboring the translocation and histologic architecture is not preserved.

PD-L1 AND FOXP3 EXPRESSION IN ORAL DYSPLASTIC TISSUES AND ORAL SQUAMOUS CELL CARCINOMA

Background Oral squamous cell carcinoma (OSCC) is an aggressive, highly immunosuppressive cancer with a high mortality rate. Interactions between programmed cell death protein 1 (PD-1; on T cells) and programmed death ligand 1 (PD-L1; on tumor cells) within the tumor microenvironment facilitates T-lymphocyte exhaustion. Regulatory T cells (Treg) are a distinct lymphocyte population, expressing the transcription factor forkhead homeobox protein-3 (FoxP3), which downregulates immune responses in OSCC.

An MST4-pβ-CateninThr40 Signaling Axis Controls Intestinal Stem Cell and Tumorigenesis

Elevated Wnt/β-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pβ-cateninThr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates β-catenin at Thr40 to block its Ser33 phosphorylation by GSK3β. Thus, MST4 mediates an active process that prevents β-catenin from binding to and being degraded by β-TrCP, leading to accumulation and full activation of β-catenin.

A Contemporary Systematic Review on Repartition of HPV-Positivity in Oropharyngeal Cancer Worldwide

Significant variation in human papillomavirus (HPV) prevalence in oropharyngeal squamous cell carcinoma (OPSCC) across countries ranging from 11% in Brazil to 74% in New Zealand has been reported earlier. The aim of this study was to systematically review the most recently published studies on the occurrence of HPV in OPSCC globally. PubMed and Embase were systematically searched for articles assessing the occurrence of HPV+ OPSCC published between January 2016 and May 2021. Studies with a study period including 2015 and the following years were included.

Pancreatic Cancer Chemotherapy Is Potentiated by Induction of Tertiary Lymphoid Structures in Mice

The presence of tertiary lymphoid structures (TLSs) may confer survival benefit to patients with pancreatic ductal adenocarcinoma (PDAC), in an otherwise immunologically inert malignancy. Yet, the precise role in PDAC has not been elucidated. Here, we aim to investigate the structure and role of TLSs in human and murine pancreatic cancer.Multicolor immunofluorescence and immunohistochemistry were used to fully characterize TLSs in human and murine (transgenic [KPC (KrasG12D, p53R172H, Pdx-1-Cre)] and orthotopic) pancreatic cancer.

Prostaglandin EP4 receptor mRNA expression in canine lymphoma

Canine lymphoma (LSA) is a diverse, aggressive malignancy initiated by a variety of factors. Understanding those factors could help identify potential treatment options. Chronic inflammation drives lymphoma in human medicine and is suspected to play a role in veterinary medicine. The exact mechanisms, however, have not been elucidated. Upregulation of the cyclooxygenase enzymes, and subsequently prostaglandins, potentially play a stimulatory role.

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