PT  - JOURNAL ARTICLE
AU  - REGINA M. HILLEBRAND
AU  - ANNABELLE VOGT
AU  - CHRISTIAN P. STRASSBURG
AU  - MARIA A. GONZALEZ-CARMONA
AU  - INGO G.H. SCHMIDT-WOLF
TI  - Immune Check Point CD40–CD40L Activates Dendritic and Effector Cells Against Human Renal Carcinoma Cells
AID  - 10.21873/anticanres.13645
DP  - 2019 Sep 01
TA  - Anticancer Research
PG  - 4643--4652
VI  - 39
IP  - 9
4099  - http://ar.iiarjournals.org/content/39/9/4643.short
4100  - http://ar.iiarjournals.org/content/39/9/4643.full
SO  - Anticancer Res2019 Sep 01; 39
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.