Adenoviral gene transfer of stromal cell-derived factor-1 to murine tumors induces the accumulation of dendritic cells and suppresses tumor growth

Abstract

The human CXC chemokine, stromal cell-derived factor 1 (SDF-1α), is known to function in vitro as a chemotactic factor for lymphocytes, monocytes, and dendritic cells. In the context that dendritic cells are powerful antigen-presenting cells, we hypothesized that adenoviral gene transfer of SDF-1α to tumors might inhibit growth of preexisting tumors through attracting dendritic cells to the tumor. AdSDF-1α mediated the expression of SDF-1α mRNA and protein in A549 cells in vitro, and the supernatant of the AdSDF-1α-infected A549 cells showed chemotactic activity for dendritic cells. When syngeneic murine CT26 colon carcinoma tumors (BALB/c) and B16 melanoma and Lewis lung cell carcinoma (C57B1/6) were injected with AdSDF-1α (5 × 108 plaque-forming units), there was an accumulation of dendritic cells and CD8+ cells within the tumor and significant inhibition of tumor growth compared with tumors injected with PBS or AdNull (control vector). The injection of AdSDF-1α into tumors induced the inflammatory enlargement and the accumulation of dendritic cells in the draining lymph node. Intratumoral AdSDF-1α administration elicited tumor-specific CTLs and adoptive transfer of splenocytes from AdSDF-1α-treated mice resulted in the elongation of survival after tumor challenge. Interestingly, in wild-type and CD4-/- mice but not in CD8-/- mice, AdSDF-1α inhibited the growth of the tumor. These observations suggest that adenoviral gene transfer of SDF-1α may be a useful strategy to accumulate dendritic cells in tumors and evoke antitumor immune responses to inhibit tumor growth. ©2006 American Association for Cancer Research.