RT Journal Article
SR Electronic
T1 Immune Check Point CD40–CD40L Activates Dendritic and Effector Cells Against Human Renal Carcinoma Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4643
OP 4652
DO 10.21873/anticanres.13645
VO 39
IS 9
A1 REGINA M. HILLEBRAND
A1 ANNABELLE VOGT
A1 CHRISTIAN P. STRASSBURG
A1 MARIA A. GONZALEZ-CARMONA
A1 INGO G.H. SCHMIDT-WOLF
YR 2019
UL http://ar.iiarjournals.org/content/39/9/4643.abstract
AB 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.