Interleukin-10 (IL-10) is a cytokine that is produced by a variety of immune cells and is known to inhibit T helper cell type 1 (T(H)1) responses, which are essential to combat tumors. In the present study, we used LSA, a T cell lymphoma cell line that expresses IL-10, to study the role of this cytokine in its tumorigenesis. To this end, LSA cells were modified to overexpress IL-10 or to block its expression via Ret-off-IL-10 vector transfection. Interestingly, blocking IL-10 expression using Ret-off-IL-10 antisense inhibited the growth of LSA in syngeneic C57BL/6 mice. Also, overexpression of IL-10 in LSA cells using Ret-off-IL-10 sense significantly increased LSA tumorigenicity. Additionally, administration of antibodies against IL-10 significantly inhibited LSA tumor growth in vivo. Together, our data stress the importance of tumor-produced IL-10 in regulating the tumorigenicity of this T cell lymphoma, and suggest that antagonizing IL-10 expression in IL-10 secreting lymphomas may have significant potential in their treatment.