The immune system is a collection of reactions and responses protecting our bodies from harm of infection and illness caused by bacteria, viruses, fungi or parasites. The body’s primary in-built protection, the

innate immunity, is always ready and prepared to act immediately. A second mechanism, the acquired immunity, learns from being exposed to diseases and creates an immune memory for future defense. These ‘good’ systems keep us healthy.

But a new study from researchers at the University of Michigan Comprehensive Cancer Center, sponsored by the National Cancer Institute, the Ovarian Cancer Research Fund, and the Marsha Rivkin Center for Ovarian Cancer Research, found that a subset of immune cells appear to be doing more harm than good.[1]

The study of MDSCs is important because it helps us to understand tumor progression and allows us toenhancethe therapeutic efficacy against cancer…

The researchers noted that these cells, called myeloid derived suppressor cells or MDSCs, also called immature myeloid cells or myeloid suppressor cells (MSCs), play a critical role during the progression of cancer and provide a niche where the cancer stem cells or CSC grow and survive.[2]

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MDSCs and CSCs are important cellular components in the cancer microenvironment and may affect cancer phenotype and patient outcome. [1]MDSCs, which can directly incorporate into tumor endothelium, secret many pro-angiogenic factors. Furthermore, MDSCs play an essential role in cancer invasion and metastasis through inducing the production of matrix metalloproteinases or MMPs, chemoattractants and creating a so-called pre-metastatic environment.[2]

Resistance to chemo and radiation
Cancer stem cells are thought to be resistant to current chemotherapy and radiation treatments, and researchers believe that killing the CSC is crucial for eliminating cancer. At the same time that these immune cells help the cancer, they also are suppressing the immune system.

More specifically, the study showed that MDSCs inhibited T-cell activation and enhanced CSC gene expression, sphere formation, and cancer metastasis. MDSCs triggered miRNA101 expression in cancer cells and subsequently repressesed the corepressor gene C-terminal binding protein-2 (CtBP2). CtBP2 then directly targeted stem cell core genes, and give, the researchers believe, cancer cells their so calledstemness,increasing metastatic and tumorigenic potential. These unique propertiesallow the cells to be so lethal. Without this immune cell, the cancer stem cells may not efficiently progress.

“[MDSC…] and its mechanisms are not good for your body and it helps the cancer by allowing the stem cells to thrive. If we can identify a therapy that targets this, we take away the immune suppression and the support for cancer stem cells. Essentially, we kill two birds with one stone,” says senior study author Weiping Zou, M.D., Ph.D., Charles B. de Nancrede Professor of surgery, immunology and biology at the University of Michigan Medical School, a worldwide leader in tumor immunology.

Ovarian cancer
The study, led by Tracy X. Cui, Ph.D., and Ilona Kryczek, Ph.D., looked at cells from the most common and lethal type of ovarian cancer, a disease in which patients often become resistant to chemotherapy, causing the cancer to return.According to recent statistics and estimates from the American Cancer Society, 22,240 Americans will be diagnosed with ovarian cancer this year and 14,030 will die from the disease.

Targeting the immune system for cancer treatment, called immunotherapy, has been well-received with many potential therapeutics currently being tested in clinical trials for a variety of cancer types.

For more information:
[1] Cui TX, Kryczek I, Zhao L, Zhao E, Kuick R, Roh MH, et al. Myeloid-Derived Suppressor Cells Enhance Stemness of Cancer Cells by Inducing MicroRNA101 and Suppressing the Corepressor CtBP2. Immunity, 2013 Sept; 39 (3).[In press; Corrected Proof]. 10.1016/j.immuni.2013.08.025 [Article]
[2] Ye XZ, Yu SC, Bian XW. Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression, angiogenesis, invasion and metastasis. J Genet Genomics. 2010 Jul;37(7):423-30. doi: 10.1016/S1673-8527(09)60061-8.[Article][PubMed]

Photo: Compared to control (left), immune cells (right) promoted tumor sphere formation, an indication of cancer stemness. Photo Courtesy/Credit: University of Michigan Comprehensive Cancer Center.

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