Blocking IL1RAP on cancer-associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1-induced neutrophil recruitment.

Background: Pancreatic ductal adenocarcinoma (PDAC) represents a major clinical challenge due to its tumor microenvironment, which exhibits immune-suppressive properties that facilitate cancer progression, metastasis, and therapy resistance. Interleukin 1 (IL-1) signaling has been implicated as a driver in this process. Mechanistically, both IL-1α and IL-1β bind to the IL-1 receptor type 1, forming a complex with IL-1-receptor accessory protein (IL1RAP), which triggers downstream signaling pathways.

Apolipoprotein A-I priming via SR-BI and ABCA1 receptor binding upregulates mitochondrial metabolism to promote insulin secretion in INS-1E cells.

Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors.

Single-cell genomics details the maturation block in BCP-ALL and identifies therapeutic vulnerabilities in DUX4-r cases.

B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) is the most common childhood malignancy and is driven by multiple genetic alterations that cause maturation arrest and accumulation of abnormal progenitor B cells. Current treatment protocols with chemotherapy have led to favorable outcomes but are associated with significant toxicity and risk of side effects, highlighting the necessity for highly effective, less toxic, targeted drugs, even in subtypes with a favorable outcome. Here, we used multimodal single-cell sequencing to delineate the transcriptional, epigenetic, and immunophenotypic characteristics of 23 childhood BCP-ALLs belonging to the BCR::ABL1+, ETV6::RUNX1+, high hyperdiploid, and recently discovered DUX4-rearranged (DUX4-r) subtypes.

Combined GLUT1 and OXPHOS inhibition eliminates acute myeloid leukemia cells by restraining their metabolic plasticity.

Acute myeloid leukemia (AML) is initiated and propagated by leukemia stem cells (LSCs), a self-renewing population of leukemia cells responsible for therapy resistance. Hence, there is an urgent need to identify new therapeutic opportunities targeting LSCs. Here, we performed an in vivo CRISPR knockout screen to identify potential therapeutic targets by interrogating cell surface dependencies of LSCs.

The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML.

Mutated nucleophosmin 1 (NPM1) is the most common genetic alteration in acute myeloid leukemia (AML), found in ∼30% of cases. Although mutations in this gene are considered favorable according to current risk stratification guidelines, a large fraction of patients will experience relapse, demonstrating the urgent need for new treatment options. Therefore, we aimed to identify cell surface proteins specifically expressed on NPM1-mutated AML cells, allowing for potential targeting with antibody-based therapies.