Determining the Lifespan of Myeloid-derived Suppressor Cells in Breast Cancer

Mentor 1

Dr. Douglas Steeber

Location

Union Wisconsin Room

Start Date

29-4-2016 1:30 PM

End Date

29-4-2016 3:30 PM

Description

Myeloid-derived suppressor cells (MDSC) are a common occurrence in cancer patients. These cells are the result of incomplete maturation of cells during hematopoiesis in the bone marrow. They function by suppressing the anti-tumor immune response, thus allowing tumors to survive and metastasize. Past research studies have focused on using a variety of strategies to eliminate these cells as an immunity boosting therapy. Surprisingly, despite the significant amount of attention MDSCs have attracted, there is a near complete lack of information concerning the lifespan of these cells. Therefore, the goal of my research project is to determine the half-life of MDSCs produced during development of breast cancer using the 4T1 mouse tumor model. Two different experimental approaches were designed, both involving labeling of MDSCs isolated from tumor-bearing mice and adoptively transferring them into recipient mice. The first approach uses BrdU to label newly produced cells in the bone marrow while the second approach uses biotinylation to label cells isolated from the spleen. At predetermined time points following transfer, recipient mice are euthanized and MDSCs identified and quantified using antibody labeling and flow cytometry. After plotting the rate of disappearance of the MDSCs, the half-life (and thus, the lifespan) can be calculated. Preliminary experiments suggest that the BrdU labeling approach will not yield enough cells to accurately follow over time. For this reason, the biotinylation approach is ongoing. Knowing the lifespan will help determine if eliminating MDSCs would be an effective treatment for cancer patients. For example, if MDSCs are found to have a short lifespan, targeting their production in the bone marrow may be an effective treatment option. Alternatively, if MDSCs have a long lifespan, simply inhibiting their production may not be enough to reduce cell numbers or the level of immunosuppression exhibited by cancer patients.

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Apr 29th, 1:30 PM Apr 29th, 3:30 PM

Determining the Lifespan of Myeloid-derived Suppressor Cells in Breast Cancer

Union Wisconsin Room

Myeloid-derived suppressor cells (MDSC) are a common occurrence in cancer patients. These cells are the result of incomplete maturation of cells during hematopoiesis in the bone marrow. They function by suppressing the anti-tumor immune response, thus allowing tumors to survive and metastasize. Past research studies have focused on using a variety of strategies to eliminate these cells as an immunity boosting therapy. Surprisingly, despite the significant amount of attention MDSCs have attracted, there is a near complete lack of information concerning the lifespan of these cells. Therefore, the goal of my research project is to determine the half-life of MDSCs produced during development of breast cancer using the 4T1 mouse tumor model. Two different experimental approaches were designed, both involving labeling of MDSCs isolated from tumor-bearing mice and adoptively transferring them into recipient mice. The first approach uses BrdU to label newly produced cells in the bone marrow while the second approach uses biotinylation to label cells isolated from the spleen. At predetermined time points following transfer, recipient mice are euthanized and MDSCs identified and quantified using antibody labeling and flow cytometry. After plotting the rate of disappearance of the MDSCs, the half-life (and thus, the lifespan) can be calculated. Preliminary experiments suggest that the BrdU labeling approach will not yield enough cells to accurately follow over time. For this reason, the biotinylation approach is ongoing. Knowing the lifespan will help determine if eliminating MDSCs would be an effective treatment for cancer patients. For example, if MDSCs are found to have a short lifespan, targeting their production in the bone marrow may be an effective treatment option. Alternatively, if MDSCs have a long lifespan, simply inhibiting their production may not be enough to reduce cell numbers or the level of immunosuppression exhibited by cancer patients.