Journal Article10.1038/ONC.2016.238
CD84 mediates CLL-microenvironment interactions
Ayelet Marom,Avital F. Barak,Matthias P. Kramer,Hadas Lewinsky,Inbal Binsky-Ehrenreich,Sivan Cohen,A Tsitsou-Kampeli,Vyacheslav Kalchenko,Yuri Kuznetsov,Vita Mirkin,Nili Dezorella,Mika Shapiro,Pamela L. Schwartzberg,Yosef Cohen,Lev Shvidel,Michal Haran,Shirly Becker-Herman,Yair Herishanu,Idit Shachar +18 more
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TL;DR: In vitro results show that CD84 expression on CLL cells interact with CD84 expressed on cells in their microenvironment, inducing cell survival in both sides, and suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.
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Abstract: Chronic lymphocytic leukemia (CLL) is a malignant disease of small mature lymphocytes. Signals from the CLL microenvironment promote progression of the disease and induce drug resistance. This phenomenon is largely dependent on direct contact between the malignant B cells and stromal cells. CD84 belongs to the signaling lymphocyte activation molecule family of immunoreceptors, which self-associates, forming an orthogonal homophilic dimer. We therefore hypothesized that CD84 may bridge between CLL cells and their microenvironment, promoting cell survival. Our in vitro results show that CD84 expressed on CLL cells interact with CD84 expressed on cells in their microenvironment, inducing cell survival in both sides. Blocking CD84 in vitro and in vivo disrupt the interaction of CLL cells with their microenvironment, resulting in induced cell death. Thus, our findings suggest novel therapeutic strategies based on the blockade of this CD84-dependent survival pathway.
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Citations
Defining the emergence of myeloid-derived suppressor cells in breast cancer using single-cell transcriptomics
Hamad Alshetaiwi,Nicholas Pervolarakis,Laura L. McIntyre,Dennis Ma,Quy H. Nguyen,Jan A. Rath,Kevin Nee,Grace A. Hernandez,Katrina Evans,Leona Torosian,Anushka Silva,Craig M. Walsh,Kai Kessenbrock +12 more
TL;DR: The MDSC-specific gene signature is established and CD84 is identified as a surface marker for improved detection and enrichment of MDSCs in breast cancers.
380
CD74 is a novel transcription regulator
Naama Gil-Yarom,Lihi Radomir,Lital Sever,Matthias P. Kramer,Hadas Lewinsky,Chamutal Bornstein,Ronnie Blecher-Gonen,Zohar Barnett-Itzhaki,Vita Mirkin,Gilgi Friedlander,Lev Shvidel,Yair Herishanu,Elias Lolis,Shirly Becker-Herman,Ido Amit,Idit Shachar +15 more
TL;DR: It is demonstrated that CD74’s cytoplasmic domain binds chromatin and regulates transcription and expression of genes involved in immune regulation, cell survival, and hematopoietic cancers and that identifying targets of CD74 will help in understanding of essential pathways regulating B-cell survival in health and disease.
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Leukaemia: a model metastatic disease
TL;DR: The key molecular processes that facilitate leukaemia metastasis in a variety of leukaemic subtypes are discussed, drawing comparisons with leukocyte trafficking and features of solid tumour invasion.
129
CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia
Hadas Lewinsky,Avital F. Barak,Victoria Huber,Matthias P. Kramer,Lihi Radomir,Lital Sever,Irit Orr,Vita Mirkin,Nili Dezorella,Mika Shapiro,Yosef Cohen,Lev Shvidel,Martina Seiffert,Yair Herishanu,Shirly Becker-Herman,Idit Shachar +15 more
TL;DR: A role for CD84 is demonstrated in the regulation of immune checkpoints by leukemia cells and CD84 blockade is identified as a therapeutic strategy to reverse tumor-induced immune suppression.
The YAP1/SIX2 axis is required for DDX3-mediated tumor aggressiveness and cetuximab resistance in KRAS-wild-type colorectal cancer.
TL;DR: Combining YAP1 inhibitors with CTX may therefore suppress DDX3-mediated tumor aggressiveness and enhance CTX sensitivity in KRAS-WT colorectal cancer.
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