101. Adenosine A(2B) receptor antagonist PSB603 suppresses tumor growth and metastasis by inhibiting induction of regulatory T cells
- Author
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Wakako, Kaji, Satomi, Tanaka, Mitsutoshi, Tsukimoto, and Shuji, Kojima
- Subjects
CD4-Positive T-Lymphocytes ,Sulfonamides ,Lung Neoplasms ,Skin Neoplasms ,Cell Survival ,Melanoma, Experimental ,Cell Differentiation ,Forkhead Transcription Factors ,CD8-Positive T-Lymphocytes ,T-Lymphocytes, Regulatory ,Adenosine A2 Receptor Antagonists ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Xanthines ,Tumor Cells, Cultured ,Animals ,Neoplasm Transplantation - Abstract
Regulatory T cells (Treg) play a role in suppression of immune response, including anti-tumor immunity. We have recently reported that treatment of naïve CD4 T cells with adenosine A(2B) receptor antagonist PSB603 under Treg-skewing conditions inhibits expression of Foxp3, a marker of differentiation to Treg, without blocking IL-2 production or CD25 expression, which are activation markers, in CD4 T cells. We hypothesized that PSB603 suppresses cancer growth and metastasis by inhibiting induction of Treg, thereby facilitating anti-tumor immunity. In this study, we first examined the effect of PSB603 on tumor growth in B16 melanoma-bearing C57BL/6 mice. Administration of PSB603 significantly suppressed the increase of tumor volume as well as the increase of Treg population in these mice. The populations of CD4 and CD8 T cells were higher and splenic lymphocyte-mediated cytotoxicity towards B16 melanoma was significantly increased in PSB603-treated mice. We confirmed that PSB603 did not reduce the viability of B16 melanoma cells in vitro. Moreover, we also examined the effect of PSB603 on tumor metastasis in pulmonary metastasis model mice intravenously injected with B16 melanoma cells. The metastasis was also suppressed in PSB603-treated mice, in which the population of Treg was significantly lower. Overall, our results suggest that A(2B) receptor antagonist PSB603 enhances anti-tumor immunity by inhibiting differentiation to Treg, resulting in a delay of tumor growth and a suppression of metastasis.
- Published
- 2014