In 2017, a projected 1.7 million people will be diagnosed with cancer, and an estimated 600 thousand people will die from it in the United States alone (1). By 2030, an expected 21.7 million new cancer cases and 13 million cancer deaths will occur worldwide (2). Due to its global prevalence and mortality, cancer demands further research and exploration.
Cancer is a disease characterized by the uncontrollable growth of cells resulting in tumors. Malignant tumors, caused by several mutations in DNA, possess the potential to metastasize to sites that are local to and distant from the primary tumor. To promote and sustain the growth of cancerous cells in tissue, tumor angiogenesis is induced, maximizing the tumor’s access to oxygen and nutrients (3).
Consequently, various white blood cells, also known as lymphocytes, target and attempt to eliminate cancerous cells. Regulatory T cells (Tregs) are a subpopulation of T lymphocytes that modulate the immune system accordingly and suppress self-reactive lymphocytes to prevent autoimmune disease (4). However, in a tumor-bearing individual, regulatory T cells inhibit the anti-tumor immune response (5). The presence of these regulatory T cells in the tumor microenvironment becomes protumorigenic as it interferes with the other lymphocytes’ ability to attack cancer cells and enables the tumor to proliferate.
Foxp3, the transcription factor responsible for the differentiation of Treg cells, is shown to be essential for Treg suppressor function. Furthermore, Foxp3 stabilizes molecular features of Treg precursor cells affecting cell function and maintenance and reverses features that are detrimental to Treg cell function (6). Therefore, the Foxp3 transcription factor is considered the most reliable marker for Tregs (7). The cellular pathway of focus that upregulates Foxp3 involves cytokine receptors. The signaling molecule IL-2 binds to the IL2RA receptor, otherwise known as the transmembrane protein CD25. This signaling activates the JAK protein, which subsequently stimulates the STAT5 protein. STAT5 increases Foxp3 (8).
Tregs expressing the transcription factor FoxP3 are highly immune-suppressive and promote tumor progression by suppressing the activation and expansion of tumor-antigen-specific effector T cells. Cancer cells recruit these Tregs in the tumor microenvironment for defense against the body’s immune system (9). High populations of Tregs in tumor tissues are frequently linked to poor prognosis; however, there is growing evidence that removal of Treg cells is able to evoke and enhance the anti-tumor immune response (5). Because of this, depletion of suppression-competent Foxp3-high effector Treg cells is currently being tested extensively and considered an effective cancer immunotherapy treatment strategy for various cancers (10).
Several studies indicate that regular exercise training increases immune competence (11). Additionally, there is now evidence suggesting that exercise reduces the risk of primary cancer development, cancer recurrence, and cancer-specific mortality (11, 12, 13). Regular exercise has also been reported to regulate, deter, and in some cases even regress the growth of tumors (14).
Prior research demonstrates that exercise has a significant impact on various aspects of cancer. However, definitive explanations regarding the mechanism by which exercise achieves these anti-tumor effects have yet to be identified. It is hypothesized that exercise influences the proliferation of specific lymphocytes in the tumor microenvironment and lymphoid tissues, thereby influencing characteristics of the cancer. This research project is concerned with the effect of exercise on regulatory T cell populations in the tumors and spleens of tumor-bearing rats. The aim of this study, as hypothesized, is to find an inverse relationship between physical activity and regulatory T cell count.
Cancer is a disease characterized by the uncontrollable growth of cells resulting in tumors. Malignant tumors, caused by several mutations in DNA, possess the potential to metastasize to sites that are local to and distant from the primary tumor. To promote and sustain the growth of cancerous cells in tissue, tumor angiogenesis is induced, maximizing the tumor’s access to oxygen and nutrients (3).
Consequently, various white blood cells, also known as lymphocytes, target and attempt to eliminate cancerous cells. Regulatory T cells (Tregs) are a subpopulation of T lymphocytes that modulate the immune system accordingly and suppress self-reactive lymphocytes to prevent autoimmune disease (4). However, in a tumor-bearing individual, regulatory T cells inhibit the anti-tumor immune response (5). The presence of these regulatory T cells in the tumor microenvironment becomes protumorigenic as it interferes with the other lymphocytes’ ability to attack cancer cells and enables the tumor to proliferate.
Foxp3, the transcription factor responsible for the differentiation of Treg cells, is shown to be essential for Treg suppressor function. Furthermore, Foxp3 stabilizes molecular features of Treg precursor cells affecting cell function and maintenance and reverses features that are detrimental to Treg cell function (6). Therefore, the Foxp3 transcription factor is considered the most reliable marker for Tregs (7). The cellular pathway of focus that upregulates Foxp3 involves cytokine receptors. The signaling molecule IL-2 binds to the IL2RA receptor, otherwise known as the transmembrane protein CD25. This signaling activates the JAK protein, which subsequently stimulates the STAT5 protein. STAT5 increases Foxp3 (8).
Tregs expressing the transcription factor FoxP3 are highly immune-suppressive and promote tumor progression by suppressing the activation and expansion of tumor-antigen-specific effector T cells. Cancer cells recruit these Tregs in the tumor microenvironment for defense against the body’s immune system (9). High populations of Tregs in tumor tissues are frequently linked to poor prognosis; however, there is growing evidence that removal of Treg cells is able to evoke and enhance the anti-tumor immune response (5). Because of this, depletion of suppression-competent Foxp3-high effector Treg cells is currently being tested extensively and considered an effective cancer immunotherapy treatment strategy for various cancers (10).
Several studies indicate that regular exercise training increases immune competence (11). Additionally, there is now evidence suggesting that exercise reduces the risk of primary cancer development, cancer recurrence, and cancer-specific mortality (11, 12, 13). Regular exercise has also been reported to regulate, deter, and in some cases even regress the growth of tumors (14).
Prior research demonstrates that exercise has a significant impact on various aspects of cancer. However, definitive explanations regarding the mechanism by which exercise achieves these anti-tumor effects have yet to be identified. It is hypothesized that exercise influences the proliferation of specific lymphocytes in the tumor microenvironment and lymphoid tissues, thereby influencing characteristics of the cancer. This research project is concerned with the effect of exercise on regulatory T cell populations in the tumors and spleens of tumor-bearing rats. The aim of this study, as hypothesized, is to find an inverse relationship between physical activity and regulatory T cell count.