invasion. These are known to arise from at least six different origins: immune cells, macrophages, adipocytes, fibroblasts, pericytes, and bone marrow mesenchymal stromal cells. Furthermore, the tumor stroma is primarily composed of the basement membrane, fibroblasts, extracellular matrix, immune cells, and blood vessels. Typically, most host cells in the stroma are characterized by tumor-suppressive abilities. However, during malignancy, the stroma will undergo alterations to consequently incite growth, invasion, and metastasis. These changes include the formation of carcinoma-associated fibroblasts (CAFs) which comprises a major portion of the reactive tissue stroma and plays a critical role in regulating tumor progression. Certain types of skin cancers (basal cell carcinomas) cannot spread throughout the body because the cancer cells require nearby stromal cells to continue their division. The loss of these stromal growth factors when the cancer moves throughout the body prevents the cancer from invading other organs. Stroma is made up of the non-malignant cells, but can provide an extracellular matrix on which tumor cells can grow. Stromal cells may also limit T-cell proliferation via nitric oxide production, hindering immune capability. Immunomodulatory effects Anti-inflammatory An important property of MSCs is their ability to suppress an excessive immune response. T-cells, B-cells, dendritic cells, macrophages, and natural killer cells can be overstimulated during an ongoing immune response, but stromal cells help to keep the balance and make sure the body can properly heal without an excessive amount of inflammation. Thereby, they also help prevent autoimmunity. MSCs can affect cells of the adaptive immune system as well as cells of the innate immune system. For example, they can inhibit the proliferation and activity of T-cells When there is a high level of MSCs during an immune response the generation of more B-cells is stunted. The B-cells that can still be produced are impacted by diminished antibody count production and chemotactic behavior. Dendritic cells in the presence of MSC's are immature and undifferentiated which causes impaired function to call upon T-cells and bridge the gap between the innate and adaptive immune responses. These dendritic cells instead release cytokines in order to regulate the growth and activity of other immune system cells as well as blood cells. Furthermore, MSCs can polarize macrophages towards a more immunosuppressive M2 phenotype. The mechanisms through which MSCs affect cells of the immune system can be contact-dependent or mediated by secreted substances. An example for a contact-dependent mechanism is the expression of programmed