By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- New research on Biotechnology is the subject of a report. According to news reporting originating from Boston, Massachusetts, by NewsRx correspondents, research stated, "In this study, we explore the hypothesis that enhanced production of lactate by tumor cells, because of high glycolytic activity, results in inhibition of host immune response to tumor cells. Lactate dehydrogenase-A (LDH-A), responsible for conversion of pyruvate to lactate, is highly expressed in tumor cells."
Our news editors obtained a quote from the research from the Harvard School of Medicine, "Lentiviral vector-mediated LDH-A short hairpin RNA knockdown Pan02 pancreatic cancer cells injected in C57BL/6 mice developed smaller tumors than mice injected with Pan02 cells. A decrease occurred in the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of mice carrying LDH-A-depleted tumors. NK cells from LDH-A-depleted tumors had improved cytolytic function. Exogenous lactate increased the frequency of MDSCs generated from mouse bone marrow cells with GM-CSF and IL-6 in vitro. Lactate pretreatment of NK cells in vitro inhibited cytolytic function of both human and mouse NK cells. This reduction of NK cytotoxic activity was accompanied by lower expression of perforin and granzyme in NK cells. The expression of NKp46 was decreased in lactate-treated NK cells. These studies strongly suggest that tumor-derived lactate inhibits NK cell function via direct inhibition of cytolytic function as well as indirectly by increasing the numbers of MDSCs that inhibit NK cytotoxicity. Depletion of glucose levels using a ketogenic diet to lower lactate production by glycolytic tumors resulted in smaller tumors, decreased MDSC frequency, and improved antitumor immune response."
According to the news editors, the research concluded: "These studies provide evidence for an immunosuppressive role of tumor-derived lactate in inhibiting innate immune response against developing tumors via regulation of MDSC and NK cell activity."
For more information on this research see: Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. Journal of Immunology, 2013;191(3):1486-95. (The American Association of Immunologists - www.aai.org; Journal of Immunology - www.jimmunol.org)
The news editors report that additional information may be obtained by contacting Z. Husain, Division of Interdisciplinary Medicine and Biotechnology, Dept. of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States. Additional authors for this research include Y. Huang, P. Seth and V.P Sukhatme (see also technology.html">Biotechnology).
Keywords for this news article include: Biotechnology, Boston, Massachusetts, United States, North and Central America.
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