Abstract 466: Does body weight influence tumor-infiltrating B cells in murine pancreatic cancer

Abstract

Abstract Background: We have developed a murine model of pancreatic cancer in congenitally obese (LepOb and LepDb) mice where tumors grow larger, metastasize, and decrease survival. Obese mice also had altered splenic T and B cells as well as downregulation of B cell and immunoglobulin genes and reduced numbers of B cells in the tumors. The question remained, however, whether alterations in tumor-infiltrating lymphocytes were a reflection of body weight or leptin metabolism. Therefore, we designed an experiment to determine whether diet-induced weight gain would alter systemic and tumor-infiltrating lymphocytes. Methods: Thirty lean C57 female mice were fed either a control 10% fat (n=10) or a 60% fat diet (n=20) starting at 6 weeks of age. At 11 weeks, all mice were inoculated with 2.5x105 PAN02 murine pancreatic cancer cells. After 6 weeks tumors that developed in 18 mice, the spleen (n=12), and the sera were harvested. Mice were categorized as Lean or Overweight if they weighed less or more than the mean final weight of the 60% fat animals (23.1g). Tumors in Lean (n=10) and Overweight (n=8) mice were sectioned and stained for B and T cells. Two observers blinded to animal weight graded cell density on a scale of 0-4 in 10 high-powered fields. Flow cytometry was performed on the spleen from Lean and Overweight mice for B, T, activated T and B (ACT), natural killer (NK) cells, and macrophages (MACRO). Serum leptin was measured. ANOVA and Student's t-test were applied. Results: Tumors were larger (1.33 vs. 0.54g, p=0.03) and leptin levels were higher (3.1 vs. 1.4ng/ml, p=0.05) in Overweight mice. Mean tumor-infiltrating lymphocyte (TIL) scores and spleen lymphocyte data are presented in the table. Conclusion: The data suggest that 1) both B and T cells are present in the pancreatic cancer microenvironment and 2) TIL and splenic lymphocyte populations do not differ between lean and overweight mice. We conclude that obesity, as opposed to overweight, is required to alter systemic and tumor microenvironment lymphocyte populations. B Cell TILT Cell TILB Cell (%) SpleenT Cell (%) SpleenACT (%) SpleenNK (%) SpleenMACRO (%) SpleenLean0.7±0.12.2±0.264±244±32.3±0.72.3±0.71.6±0.2Overweight0.7±0.12.0±0.258±139±51.5±0.31.4±0.41.4±0.3 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 466.