What is being tested is how acute exercise can affect MDSC levels in mice during early tumor progression.
By: Jacob Garritson, Kanika Hicks, and Molly Briggle
ABSTRACT
A majority of cancer research is a search for the cure; there has been less time dedicated to coping with treatments. That's why research on exercise’s effects on MDSCs was chosen. It's not a cure but it can help patients handle treatment. The MDSCs are necessary to regulating the immune system, but they need to be regulated as well. They regulate T cells and other natural killer cells. T cells are the main line of defense when it comes to irregular cells or foreign invaders. They also help activate the production of antibodies, which is essential to fighting off cancer. Exercise is an interest because it helps the immune system. Moderate exercise controls inflammation which in turn controls tumor growth giving time for the immune system to do its job. The study hopes to prove that exercise can help patients get through their treatments, especially immunotherapy, quicker and healthier.
INTRODUCTION
Scientists have searched high and low for a cure of cancer and why it exists. They have often wondered why cancer can overcome even the most healthy human’s body and whether or not a person’s lifestyle can increase a person’s risk of cancer. To be able to understand this paper, it is important to know what myeloid-derived suppressor cells (MDSC) and T cells are, and how they function. MDSC cells are a family of cells that originate from stem cells in the bone marrow. These cells multiply during chronic infection or during cancer, andpossess immunosuppressive qualities which are essential to the immune system. Studying the effects of exercise on the immune system, which fights cancer, is essential to understanding how we can better help cancer patients. By following this line of thought, we are lead to the question: how does exercise affect cancer?
INTRODUCTION
Scientists have searched high and low for a cure of cancer and why it exists. They have often wondered why cancer can overcome even the most healthy human’s body and whether or not a person’s lifestyle can increase a person’s risk of cancer. To be able to understand this paper, it is important to know what myeloid-derived suppressor cells (MDSC) and T cells are, and how they function. MDSC cells are a family of cells that originate from stem cells in the bone marrow. These cells multiply during chronic infection or during cancer, andpossess immunosuppressive qualities which are essential to the immune system. Studying the effects of exercise on the immune system, which fights cancer, is essential to understanding how we can better help cancer patients. By following this line of thought, we are lead to the question: how does exercise affect cancer?
INTRODUCTION
Scientists have searched high and low for a cure of cancer and why it exists. They have often wondered why cancer can overcome even the most healthy human’s body and whether or not a person’s lifestyle can increase a person’s risk of cancer. To be able to understand this paper, it is important to know what myeloid-derived suppressor cells (MDSC) and T cells are, and how they function. MDSC cells are a family of cells that originate from stem cells in the bone marrow. These cells multiply during chronic infection or during cancer, andpossess immunosuppressive qualities which are essential to the immune system. Studying the effects of exercise on the immune system, which fights cancer, is essential to understanding how we can better help cancer patients. By following this line of thought, we are lead to the question: how does exercise affect cancer?
METHODS AND MATERIALS
Six female BALB/c mice, which were 8 weeks old, were housed individually in a temperature-controlled facility; the facility was on a 12-12 hour light-dark cycle. Randomly, the mice were selected and assigned equally to two groups: sedentary tumor (SED) and exercise tumor (EX). The EX group were given wheels mounted in their cages 24 hours every day three weeks prior to tumor cell injection. After tumor inoculation, they ran twelve additional days. The SED mice were restricted to normal cage activity while we performed the study. The cells used in the experiments were syngeneic 4T1 mouse carcinoma cell line; orthotopic tumors were grown in the mammary gland from this cell line. This cell line was selected because these tumors quickly attracted MDSCs that were detectable in the spleen. The 4T1 cells were grown in RPMI growth medium. Using a lethal injection of heparinized Euthasol solution, the mice were euthanized on the fifth week. Samples were taken from the spleen, blood and tumor and prepared to undergo flow cytometry. The spleens were weighed and mechanically dissociated. The blood was collected by cardiac puncture from the spleen, tumor and blood. The tumors were removed, weighed and homogenized. PMN-MDSCs and M-MDSCs from tumor bearing mice’s spleens were prepared for functional assessment.
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Materials:
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Six female Balb/c mice
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4T1 mouse carcinoma cells
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PBS-1% BSA buffer
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RPMI medium
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FBS
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Centrifuge
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Attune NxT flow cytometer
RESULTS AND DISCUSSION
Fig #1: Distances ran
The mice all ran considerable distances. The exercised participants running distances were all recorded. There was increased activity at night. These results are just beginning to show the gentle decrease in exercise exhibited by the specimens, before euthanasia.
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After the mice were euthanized, the samples were harvested and studied. The results showed clear development of tumor in the spleen and mammary glands. The data shows the EX mice have smaller tumors and smaller spleens. Both of these support the hypothesis. The spleen stores/ filters the blood and helps fight infection. A smaller spleen essentially means there is less infection to fight off, which is true since the EX have smaller tumors.
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We tested the spleen and mammary samples; the outcome presented higher MDSC cells in the unexercised specimens. While the exercised mihad higher levels of MDSCs at the tumor site, they were much lower through the rest of the body. In EX mice, higher MDSC levels at the cancer site and nowhere else could mean the cancer is not metastasizing.
Fig #2: Tumor and Spleen Mass
Fig #3: MDSC Proportions
INTRODUCTION
ACKNOWLEDGMENTS
Jacob Garritson
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Lori Ball
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Reba Zimmerle
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All of the FSI staff
