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Immunosuppressive mechanisms in myeloid cells
Published on December 2, 2014 49 min
Other Talks in the Series: Immunotherapy of Cancer
Immunotherapy in neuroendocrine tumors 2 - role of immunotherapy
- Dr. Nitya Raj
- Memorial Sloan Kettering Cancer Center, USA
Immune checkpoint blockade in CNS tumors
- Dr. Md. David A. Reardon
- Center for Neuro-Oncology Dana-Farber Cancer Institute, USA
Hi. My name is Dimitry Gabrilovich. I am head of the Tumor Immunology Program in Wistar Institute and Professor to University of Pennsylvania in Philadelphia. I am going to talk to you about myeloid-derived suppressor cells in tumors.
What we'll discuss, the following topics today. First, we will discuss a definition of myeloid-derived suppressor cells, then the main characteristics, followed by molecular mechanisms regulating myeloid-derived suppressor cell expansion, and mechanism of myeloid-derived suppressor cell activity, primarily, the inhibitory effect on T cells. We will talk about therapeutic targeting of myeloid-derived suppressor cells in cancer at the end of the presentation.
Myeloid cells with immunosuppressive features have been known since the late '70s. Investigators describe appearances of these cells in response to stimulation with different growth factors. The first evidence that these cells could be involved in tumor development or associated with the tumor development have been recorded in mid-90s. And they become the focus of more intensive studies in early 2000. The term of myeloid-derived suppressor cells has been introduced in 2007. And these days, these cells become the focus of intensive studies by many groups in different conditions, primarily in cancer.
As we know, myeloid cells differentiate in bone marrow through the sequential steps involved in several different progenitors from hematopoietic stem cells through the common myeloid progenitors, and they end up in three major classes of terminally differentiated mature myeloid cells, neutrophils, or granulocytes, some macrophages, or dendritic cells. In cancer, tumor and tumor-associated stroma produce multiple different cytokines which dramatically affect differentiation of myeloid cells. The end result of this process is accumulation, in some cases, dramatic accumulation, of cells which are characterized myeloid lineages, but also, the relatively immature phenotype and a very important ability to suppress immune function; therefore, the cell, so-called myeloid-derived suppressor cells. And I will refer to them as MDSC for simplicity in the next slides.