TY - JOUR T1 - Immune Check Point CD40–CD40L Activates Dendritic and Effector Cells Against Human Renal Carcinoma Cells JF - Anticancer Research JO - Anticancer Res SP - 4643 LP - 4652 DO - 10.21873/anticanres.13645 VL - 39 IS - 9 AU - REGINA M. HILLEBRAND AU - ANNABELLE VOGT AU - CHRISTIAN P. STRASSBURG AU - MARIA A. GONZALEZ-CARMONA AU - INGO G.H. SCHMIDT-WOLF Y1 - 2019/09/01 UR - http://ar.iiarjournals.org/content/39/9/4643.abstract N2 - Background/Aim: Adenoviral-mediated expression of CD40 ligand (CD40L) on dendritic cells (DCs) activates immune check point CD40/CD40L, enhancing the immunostimulation of DCs and effector cells against human renal carcinoma cells (RCC) and inducing tumor cell apoptosis in vitro. Materials and Methods: DCs, isolated from buffy coats from healthy donors, were transduced with adenoviruses carrying human CD40L (Ad-hCD40L). Subsequently maturation marker and cytokine expression were analyzed by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay. Results: Adenoviral transduction induced high expression of soluble CD40L and membrane-bound CD40L, leading to a strong CD40–CD40L interaction in DCs. Interestingly, a T-helper cell type 1 shift of expressed cytokines/chemokines was observed due to the expression of membrane-bound CD40L rather than due to soIuble CD40L alone, which significantly reduced immunoactivation of DCs. However, supernatants of Ad-hCD40L-transduced DCs induced apoptosis of RCC cells. Co-culture of Ad-hCD40L DCs with cytokine-induced killer cells led to a significant stimulation of tumor-specific cytokine-induced killer cells, with increased proliferation and cytotoxicity. Conclusion: Use of Ad-hCD40L-transduced DCs is a promising approach to treating RCC. ER -