Publications by authors named "Ilona Berestjuk"
Article Synopsis
- Tumor progression leads to fibrosis, which involves excessive buildup of extracellular matrix and reduces immune cell infiltration, particularly affecting CD8 T cells.
- Tumor-associated macrophages (TAMs) adapt to the stiff fibrotic environment by promoting collagen production through signaling from transforming growth factor-β.
- This collagen production by TAMs creates a challenging metabolic environment that limits the effectiveness of CD8 T cells, hindering their ability to mount strong antitumor responses in breast cancer patients.
Unlabelled: Fibroblastic reticular cells (FRC) are immunologically specialized myofibroblasts that control the elasticity of the lymph node, in part through their contractile properties. Swelling of tumor-draining lymph nodes is a hallmark of lymphophilic cancers such as cutaneous melanoma. Melanoma displays high intratumoral heterogeneity with the coexistence of melanoma cells with variable differentiation phenotypes from melanocytic to dedifferentiated states.
View Article and Find Full Text PDFLineage dedifferentiation toward a mesenchymal-like state displaying myofibroblast and fibrotic features is a common mechanism of adaptive and acquired resistance to targeted therapy in melanoma. Here, we show that the anti-fibrotic drug nintedanib is active to normalize the fibrous ECM network, enhance the efficacy of MAPK-targeted therapy, and delay tumor relapse in a preclinical model of melanoma. Acquisition of this resistant phenotype and its reversion by nintedanib pointed to miR-143/-145 pro-fibrotic cluster as a driver of this mesenchymal-like phenotype.
View Article and Find Full Text PDFArticle Synopsis
- There is a big problem with treatments for advanced melanoma when patients have a specific mutation called BRAF, which makes the therapy not work as well as hoped.
- A part of the environment around the tumor, called the extracellular matrix (ECM), helps the tumors resist these treatments and helps them survive.
- By studying how tumors adapt, scientists found that targeting certain proteins (DDR1 and DDR2) in the ECM can make treatments more effective and slow down the growth of the tumors.
Cladribine is an oral synthetic purine analog that depletes lymphocytes and induces a dose-dependent reduction of T and B cells. It was approved for the therapy of highly active relapsing-remitting multiple sclerosis. Given cladribine's mechanism of action, an increased risk of malignancies was suspected from the number of cancers that occurred in the 3.
View Article and Find Full Text PDFAberrant extracellular matrix (ECM) deposition and stiffening is a physical hallmark of several solid cancers and is associated with therapy failure. BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that is frequently associated with transcriptional reprogramming and a de-differentiated cell state. Melanoma cells secrete their own ECM proteins, an event that is promoted by oncogenic BRAF inhibition.
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