The immune status of the tumor microenvironment is a key
indicator determining the antitumor effect of
immunotherapy. Oncolytic viruses directly target
tumor cells or indirectly modulate the tumor microenvironment (TME) especially when properly armed. It was previously demonstrated that conditionally replicating adenovirus serotype 5 (CRAd5) encoding
tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) had outstanding antitumor effects in different human
cancer cells xenograft models; however, its antitumor immune mechanism has not been evaluated in immunocompetent preclinical mouse models. We first explored the antitumor activity of CRAd5-TRAIL in several murine
tumor models and found that the expression of TRAIL induced increases or activation in
tumor-infiltrating T cells. To further improve the antitumor effects, mouse
CD40 ligand (mCD40L) as an immune activator expressed by recombinant Ad5 vector was firstly used in combination with CRAd5-TRAIL for
tumor immunotherapy. Both in vitro and in vivo studies demonstrated that mCD40L effectively activated dendritic cells (DCs), B cells, and
tumor-infiltrating T cells, and also promoted
tumor cell apoptosis by increasing the expression of
TRAIL receptors, thereby significantly enhancing the antitumor activity of oncolytic adenoviruses in CT26 and B16
tumor-bearing models. Although affected by the restriction of oncolytic adenovirus replication in mouse cells, the combination treatment failed to completely eliminate
tumor cells, our research still provided a promising strategy for oncolytic adenovirus-mediated solid
tumor immunotherapy.