Navigation Links
Moffitt researchers say silencing of retinoblastoma gene regulates differentiation of myeloid cells

Researchers at the Moffitt Cancer Center have found a potential mechanism by which immune suppressive myeloid-derived suppressor cells can prevent immune response from developing in cancer. This mechanism includes silencing the tumor suppressor gene retinoblastoma 1 or Rb1. Their data explains a new regulatory mechanism by which myeloid-derived suppressor cells are expanded in cancer.

Their study appeared in a recent issue of Nature Immunology.

According to the authors, two kinds of myeloid-derived suppressor cells - monocytic M-MDSCs and granulocytic PMN-MDSCs - regulate immune responses in cancer and other conditions. In experiments with tumor-bearing mice, they discovered that M-MDSCs acquire some of the physical characteristics of PMN-MDSCs. Acquisition of the PMN-MDSCs characteristics, they found, was "mediated" by the silencing of Rb1 by modifications in a histone deacetylase 2 (HDAC-2), an enzyme decoded by the HDAC2 gene.

"Our findings demonstrate the function of a newly discovered regulatory mechanism of myeloid cells in cancer," said study lead author Dmitry I. Gabrilovich, M.D., senior member of Moffitt's Immunology Program.

According to study first author Je-In Youn, Ph.D., a post-doctoral fellow in the Gabrilovich laboratory, Rb1 is among members of the retinoblastoma family of transcription regulators that integrate multiple cellular signals to control cell proliferation and differentiation. In their experiments, the researchers found that when Rb1 was deficient in tumor-bearing mice it indicated a direct role for Rb1 in regulating M-MDSC differentiation toward PMN-MDSCs.

Their data suggested that Rb1 silencing could be initiated by HDAC-2 which, said Youn, is known to be involved in modulating the repressive activity on promoters of certain genes involved in cell differentiation.

They proposed that, in tumors, a large portion of M-MDSCs acquire the ability to differentiate into PMN-MDSCs and that it "appears that, in cancer, M-MDSCs probably acquire the ability to differentiate into PMN-MDSCs" and "may represent an important pathways for the accumulation of these cells in contrast to normal monocytes."

"We demonstrated that HDAC-2 can directly interact with Rb1 promoter and participate in silencing Rb1 expression," said study co-author Vinit Kumar, Ph.D., also a post-doctoral fellow in the Gabrilovich laboratory. He added that "silencing Rb1 expression in monocytes and other myeloid progenitors may be critical to the accumulation of PMN-MDSCs."

"If the role of HDAC-2 in this process is confirmed, the finding may offer an opportunity for therapeutically targeting myeloid cells in cancer and possibly in other pathologic conditions," concluded the researchers.


Contact: Kim Polacek
H. Lee Moffitt Cancer Center & Research Institute

Related medicine news :

1. Moffitt researchers find cancer therapies affect cognitive functioning among breast cancer survivors
2. Moffitt Cancer Center researchers: Quality of life as important as quantity of life
3. Moffitt Cancer Center researchers working at frontiers of melanoma research
4. Moffitt researchers find adolescents with cancer concerned about their future reproductive health
5. Moffitt researcher publishes book on nutritional management of cancer treatment effects
6. Moffitt researcher awarded GE grant to develop tool to detect breast cancer metastasis genetic risks
7. Researchers creating designer lymph nodes based on Moffitts Total Cancer Care initiative
8. Moffitt Cancer Center researchers identify drivers of sarcoma growth and survival
9. Moffitt Cancer Center researchers develop and test new anti-cancer vaccine
10. Moffitt researcher, colleagues find success with new immune approach to fighting some cancers
11. Moffitt researchers: Darwins principles say cancer will always evolve to resist treatment
Post Your Comments:
(Date:11/27/2015)... ... 2015 , ... The print component of “Supporting Our Caregivers” ... New York, Minneapolis, South Florida, with a circulation of approximately 250,000 copies and ... vast social media strategy and across a network of top news sites and ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... A simply ... Jones, is an interesting show that delves into an array of issues that are ... that could benefit from open dialogue, this show is changing the subjects consumers focus ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... Dr. ... Medical Associates, Inc. and Dr. Tucker Bierbaum with Emergency Medicine at St., ... observed that both STEMI and Sepsis conditions present in similar ways and require time-critical ...
(Date:11/26/2015)... ... November 26, 2015 , ... CognisantMD and Cambridge ... imaging in the Waterloo region. Using the Ocean Platform, family physicians can now ... their electronic medical record (EMR) without the need for redundant patient entry or ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... opinion process, participated in the 61st annual Employee Benefits Conference. The Employee Benefits ... place Sunday, November 8th through Wednesday, November 11th, 2015. The conference was held ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... Nov. 26, 2015  The total global healthcare industry is ... 2015-2016. Latin America has the highest ... (excluding Japan ), is second with growth ... to face increased healthcare expenditure. In 2013-2014, total government funded ... 43.5% in 2008-2009 to 41.2% in 2013-2014. In real terms, ...
(Date:11/25/2015)... , Nov. 25, 2015 AAIPharma Services ... investment of at least $15.8  Million to expand ... Wilmington, NC . The expansion will provide ... meet the growing demands of the pharmaceutical and ... site expansion will provide up to 40,000 square ...
(Date:11/25/2015)... 2015 Kitov Pharma ceuticals ... a biopharmaceutical company focused on the development of therapeutic ... today announced the closing of its previously announced underwritten ... ), each representing 20 ordinary shares of the Company, ... ADSs and warrants were issued in a fixed combination ...
Breaking Medicine Technology: