Abstract 413: Involvement of myeloid derived suppressor cells (MDSC) in the changes of plasma amino acid profiles in cancer disease

Abstract

Abstract Although maintained in healthy human, it is well known that plasma amino acid profiles are changed in various pathologic conditions, including liver disorder and cancer. We have previously reported the potential use of plasma amino acid profiling as diagnosis for several cancer disease. However, some questions remained for the mechanisms. The changes in plasma amino acid profiles in tumor disease were regulated by a lot of factors, including metabolic changes of tumors and immune cells. In this study, we focused on the role of immune cells, especially myeloid derived suppressor cells (MDSC). MDSC are characterized as immature myeloid cells that are precursors of dendritic cells, macrophages, and/or granulocytes, they are considered to accumulate in the blood, lymph nods, and at tumor sites in most patients and experimental animals with cancer and inhibit anti-tumor inflammation. Therefore we hypothesized that MDSC were involved in the changes in plasma amino acid profiles in tumor disease. To test our hypothesis, we employed C57BL/6 mice tumor model in which Lewis lung carcinoma (3LL) was injected subcutaneously. Using flow cytometry analysis, a significant percentage of MDSC were detected in spleens of tumor-bearing mice as compared to control normal mice. To assess the role of MDSC in the changes in plasma amino acid profile, we eliminated MDSC from the tumor-bearing mice by inducing apoptosis cell death on MDSC selectively in vivo. Flow cytometry results showed a significant decrease in the percentage of CD11b+ Gr1+ cells in splenocytes derived from MDSC deleted tumor-bearing mice as compared to tumor-bearing mice. To study the immunogenic effects of the MDSC deletion on the tumor-bearing mice, we performed histological analysis (H&E staining) and extensive areas of inflammation within 3LL subcutaneous tumors were observed after the MDSC deletion. In addition, we investigated the effects of the MDSC deletion on the percentage of splenic T cell subpopulations by Flow cytometry. The percentage of CD4+ and CD8+ T cells were increased in spleens of MDSC deleted tumor-bearing mice compared to untreated tumor-bearing mice. To evaluate the effects of the MDSC depletion on the plasma amino acid profiles, plasma samples were collected from normal mice, tumor-bearing mice, and MDSC deleted tumor-bearing mice. Plasma amino acid concentration were measured by LC-MS. The MDSC deletion significantly changed the concentrations of some amino acids in plasma compared to the untreated tumor-bearing mice and normal mice. These changes in plasma amino acid concentrations were partially impeded by adoptive transfer of MDSC from tumor-bearing mice. Altogether, these results suggest that MDSC may be involved in the changes in plasma amino acid profiles in tumor disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 413. doi:10.1158/1538-7445.AM2011-413