Abstract 504: Acarbose enhances intratumoral CD8 T cell responses in a pre-clinical model of kidney cancer

Abstract

Abstract Metastatic renal cell carcinoma (RCC) exhibits high mortality rates and chemotherapeutic resistance. Treatment options include immune-stimulatory therapies, such as high-dose IL-2 and anti-PD-1; however, these agents only generate responses in 20-50% of patients. This illustrates the need to find ways to improve patient response rates. Long-term caloric restriction (CR) extends longevity and reduces cancer risk in animal studies. Caloric restriction mimetics (CRMs), which replicate the benefits of CR without reductions in calorie intake, were recently found to enhance chemotherapeutic efficacy by improving CD8 T cell mediated anti-tumor immunity. Here we examined acarbose, an FDA-approved anti-diabetic agent with CRM properties, in a preclinical model of kidney cancer. BALB/c mice were orthotopically tumor challenged with syngeneic luciferase-expressing Renca renal carcinoma cells, which spontaneously metastasize to the lungs. Mice were then randomized to either an acarbose-supplemented or control diet. Compared to mice on control diet, acarbose did not alter renal tumor progression at Day 28. Importantly, acarbose did not exacerbate weight loss associated with renal tumor growth. Flow cytometric analysis at Day 28 revealed increased frequencies of activated (CD44+CD62L-) intra-tumoral CD8 T cells in mice on acarbose (p=0.012). Additionally, renal tumors from mice on acarbose displayed increased frequencies of early effector (CD127-KLRG1-) CD8 T cells, in addition to heightened frequencies of PD-1+ CD8s. These findings suggest that acarbose exhibits immune-modulatory properties which could promote anti-tumor immunity. Future experiments will focus on elucidating mechanisms contributing to alterations in anti-tumor immunity. Importantly, these studies warrant investigating acarbose in combination with currently available treatments as a potentially novel therapeutic adjuvant. Citation Format: Rachael M. Orlandella, Daniel L. Smith, Lyse A. Norian. Acarbose enhances intratumoral CD8 T cell responses in a pre-clinical model of kidney cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 504.