Spatial Determination of Immune Suppressor Cells and T Cell Populations in a Murine Breast Cancer Model
Mentor 1
Douglas Steeber
Location
Union Wisconsin Room
Start Date
29-4-2016 1:30 PM
End Date
29-4-2016 3:30 PM
Description
Cancer patients often develop large populations of inhibitory immune cells such as myeloid derived suppressor cells (MDSCs) and T regulatory cells. These inhibitory immune cells are known to suppress the anti-tumor T cell response resulting in tumor growth and metastasis. My current research focuses on defining the distribution of T cytotoxic cells, T helper cells and T regulatory cells with relation to MDSC clusters and hypoxia in the 4T1 model of murine breast cancer. Previous studies in our lab showed MDSCs proliferate, form large aggregates and colocalize to regions of hypoxia within the tumor. Additionally, MDSCs are known to stimulate T regulatory production, suggesting interaction between these cell populations. However, during tumor development immunohistochemical analysis showed that T regulatory cells were distributed throughout the tumor and did not colocalize with MDSCs. In late stage tumors, MDSC clusters increased in size and remained localized near hypoxic areas. Similarly, T regulatory cells increased in number but remained distributed throughout the tumor. Since T regulatory cells and MDSCs inhibit T helper and T cytotoxic cell function, the relative distribution of these cell populations was also examined. Surprisingly, T helper cells were found to be in higher concentrations away from the MDSC clusters and hypoxic regions. The T cytotoxic cell response, which was predominant in the later stage tumors, showed similar distribution to T helper cells. Furthermore, T regulatory cells did not show specific colocalization with these other T cell populations. Therefore, no direct interactions between the suppressor populations and conventional T cell populations were identified. Future studies will examine early stage tumors to determine whether interactions among these cell populations occur initially following tumor development and are lost at later stages.
Spatial Determination of Immune Suppressor Cells and T Cell Populations in a Murine Breast Cancer Model
Union Wisconsin Room
Cancer patients often develop large populations of inhibitory immune cells such as myeloid derived suppressor cells (MDSCs) and T regulatory cells. These inhibitory immune cells are known to suppress the anti-tumor T cell response resulting in tumor growth and metastasis. My current research focuses on defining the distribution of T cytotoxic cells, T helper cells and T regulatory cells with relation to MDSC clusters and hypoxia in the 4T1 model of murine breast cancer. Previous studies in our lab showed MDSCs proliferate, form large aggregates and colocalize to regions of hypoxia within the tumor. Additionally, MDSCs are known to stimulate T regulatory production, suggesting interaction between these cell populations. However, during tumor development immunohistochemical analysis showed that T regulatory cells were distributed throughout the tumor and did not colocalize with MDSCs. In late stage tumors, MDSC clusters increased in size and remained localized near hypoxic areas. Similarly, T regulatory cells increased in number but remained distributed throughout the tumor. Since T regulatory cells and MDSCs inhibit T helper and T cytotoxic cell function, the relative distribution of these cell populations was also examined. Surprisingly, T helper cells were found to be in higher concentrations away from the MDSC clusters and hypoxic regions. The T cytotoxic cell response, which was predominant in the later stage tumors, showed similar distribution to T helper cells. Furthermore, T regulatory cells did not show specific colocalization with these other T cell populations. Therefore, no direct interactions between the suppressor populations and conventional T cell populations were identified. Future studies will examine early stage tumors to determine whether interactions among these cell populations occur initially following tumor development and are lost at later stages.
