Publications by authors named "Joanna H Maltbaek"
Article Synopsis
- cGAS is a DNA sensor that plays a crucial role in the immune response against viruses and tumors by producing cGAMP, which activates STING to trigger antiviral responses.
- Recent findings show that cGAMP can be exported from cells, and ABCC1 has been identified as the primary protein responsible for this export process.
- Overexpression of ABCC1 reduces STING signaling by promoting cGAMP export, while its deficiency can lead to heightened STING signaling and worsen autoimmune conditions, highlighting its role in regulating immune responses.
Article Synopsis
- Gastrointestinal stromal tumors (GISTs) are the most common type of sarcoma found in the gastrointestinal tract, primarily caused by mutations in the KIT receptor tyrosine kinase, specifically the exon 11 KIT V559Δ mutation.
- Imatinib is a key treatment for GIST, but patients often develop resistance due to mutations like KIT V654A, prompting the need for alternative therapies.
- Researchers created a mouse model with the double KIT mutation (V558Δ;V653A) to study its effects, finding that this mutation increased tumor growth and resistance to imatinib while showing better response to the drug cabozantinib.
Detection of intracellular DNA by the cGAS-STING pathway activates a type I interferon-mediated innate immune response that protects from virus infection. Whether there are additional DNA sensing pathways, and how such pathways might function, remains controversial. We show here that humans-but not laboratory mice-have a second, potent, STING-independent DNA sensing pathway (SIDSP).
View Article and Find Full Text PDFIntroduction: Murine Kupffer cells (KCs) comprise CD11bhi and F4/80hi subsets. Tissue-resident macrophages are known to express the tyrosine kinase receptors colony-stimulating factor 1 receptor (Csf1r) and Mer. However, the expression of Csf1r and Mer on KC subsets and the importance of these tyrosine kinases during liver regeneration (LR) are unknown.
View Article and Find Full Text PDFArticle Synopsis
- Gastrointestinal stromal tumor (GIST) is a type of cancer that starts from a mutation in a gene that helps control cell growth.
- In studies with mice and humans, certain immune cells (dendritic cells) were found to help T cells fight the tumor, but treatment with a drug called imatinib (used to fight GIST) can reduce these helpful cells over time.
- The study also discovered that keeping these immune cells around while using imatinib could make the treatment more effective against the tumor.
Tyrosine kinase inhibition of gastrointestinal stromal tumors (GIST) is effective but typically culminates in resistance and is rarely curative. Immunotherapy has potential application to GIST, as we previously showed that T-cell checkpoint blockade increases the antitumor effects of imatinib. Here, we showed that ligation of CD40 using an agonistic antibody (anti-CD40) activated tumor-associated macrophages (TAMs) in a knock-in mouse model of GIST harboring a germline mutation in exon 11.
View Article and Find Full Text PDFGastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a or mutation. However, the molecular basis for tumor malignancy is not well defined. Although the Wnt/β-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain.
View Article and Find Full Text PDFPurpose: Tyrosine kinase inhibitors are effective in gastrointestinal stromal tumors (GISTs) but often are of transient benefit as resistance commonly develops. Immunotherapy, particularly blockade of the inhibitory receptor programmed death 1 (PD-1) or the ligand programmed death ligand 1 (PD-L1), has shown effectiveness in a variety of cancers. The functional effects of PD-1/PD-L1 blockade are unknown in GISTs.
View Article and Find Full Text PDF