Abstract 2877: Exercise, alone and in combination with a whole tumor cell vaccine reduces mammary tumor cell growth and enhances anti-tumor immunity
Authors: Turbitt William J. , Sosnoski Donna , Mastro Andrea , Rogers Connie 
Published: August 2015

Abstract
Regular, moderate exercise (EX) can reduce both the incidence and recurrence of breast cancer (BC), and improve survival. Numerous biological mechanism(s) have been proposed to explain these beneficial clinical effects of EX. However, little work has been done to examine the effect of EX on immunomodulation, i.e. the balance between anti-tumor immunity and the emergence of immunosuppressive cells, in particular myeloid derived suppressor cells (MDSC). We have previously demonstrated that moderate EX significantly enhances antigen-specific CD4+ and CD8+ T cell responses and reduces regulatory T cell function in tumor free-mice. Thus, the goal of the current study was to determine if EX could enhance effector function and reduce immunosuppression in tumor bearing mice, and determine if there were any synergistic effects of EX and the administration of a whole tumor cell vaccine on the aforementioned outcomes. Female Balb/c mice were randomized into EX or sedentary control (SED) groups (n = 14-16/group) and had access to running wheel or standard cages, respectively, for 12 weeks prior to the injection of 5×10^4 lucerifase-transfected 4T1.2 tumor cells into the 4th mammary fat pad. Mice were further randomized into vaccination (n = 6-8/group) or vehicle control (n = 4/group) and administered 1×10^6 irradiated 4T1.2 cells (VAC) or HBSS (VEH) at day 7, 14, 21, and 28 post tumor injection. All mice were fed the AIN-76A diet; however, the EX mice (n = 14) were fed 90% of caloric intake of SED animals to remain in energy balance (prevent weight gain) over the course of the study. Primary tumor growth was quantified, and at sacrifice (day 35) organs were collected to assess the following endpoints: splenic antigen-specific CD8+ effector function and myeloid derived suppressor cell (MDSC) accumulation, and metastatic burden in femurs. EX mice, with or without vaccine, weighed significantly less than SED mice (p&lt;0.001). There was a significant effect of both vaccination and EX on primary tumor growth (F(24,200) = 7.386, p&lt;0.001), splenic IFN-γ production (KW = 11.43, p = 0.010); and the accumulation of MDSC (F(3,28) = 6.486, p = 0.021). However, there was only an EX effect on metastatic burden (p = 0.027). There was a synergistic effect of the combination of vaccine+EX on tumor growth, but no other endpoint. These results demonstrate that exercise alone (i.e. in a prevention model, 12 weeks prior to tumor implantation) is highly effective in reducing primary tumor growth and metastases in an aggressive tumor, and significantly shifted the balance of effector and immunosuppressive factors in the direction of anti-tumor immunity. Furthermore, these results demonstrate that exercise is a viable intervention that may yield significant clinical benefit when used in combination with therapeutic cancer vaccines. This work is supported by internal PSU pilot funds for CJR; T32AI074551-03 for WJT.
Citation Format: William J. Turbitt, Donna Sosnoski, Andrea Mastro, Connie Rogers. Exercise, alone and in combination with a whole tumor cell vaccine reduces mammary tumor cell growth and enhances anti-tumor immunity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2877. doi:10.1158/1538-7445.AM2015-2877