Murine L5178Y T-cell lymphoma cells prime macrophages via CD40-CD40L interaction to mediate LPS-activated antitumor effects in vitro (50.13)

Abstract

Abstract We present that L5178Y murine T-cell lymphoma cells can prime naïve murine macrophages (Mϕ) to subsequent LPS stimulation, resulting in antitumor effects in vitro against L5178Y cells. Priming occurred in both cell-type and TLR specific manner, as L5178Y tumor cells (TC), but not naïve splenocytes, primed Mϕ to ligation of TLR4 but not TLR9. L5178Y-primed Mϕ also showed down-regulation of CD40 and CD86 and up-regulation of B7H1, with no changes of TLR4, B7H4, NKG2D and MHC-II expression. Among different TC lines, the priming effect was limited to murine TC of T cell (L5178Y and YAC-1) but not B cell (A20) or nonmyeloid (B16) origin. Human TC lines including Jurkat (T cell), Daudi (B cell), and M21 (melanoma) failed to substantially prime Mϕ. Neither L5178Y-conditioned supernatants nor co-culture of Mϕ and L5178Y TC in transwells resulted in priming, indicating that direct L5178Y TC-Mϕ contact was needed. Furthermore, TLR4-ligation must not precede contact with L5178Y TC in order to induce tumoritoxic Mϕ. Among several receptor-ligand pairs reciprocally expressed on Mϕ and L5178Y TC and potentially involved in the Mϕ priming, CD40 (expressed on Mϕ) and CD40L (expressed on L5178Y TC) appeared to play the most important role, as blocking their interaction with anti-CD40L mAb substantially reduced in vitro tumoritoxicity. Hence, contact with TC may facilitate Mϕ-mediated immune surveillance against certain cancers.