Dendritic Cell-Based Immunotherapy for Solid Tumors

Abstract

As a treatment for solid tumors, dendritic cell (DC)-based immunotherapy has not been as effective as expected. Here, we review the reasons underlying the limitations of DC-based immunotherapy for solid tumors and ask what can be done to improve immune cell-based cancer therapies. Several reports show that, rather than a lack of immune induction, the limited efficacy of DC-based immunotherapy in cases of renal cell carcinoma (RCC) likely results from inhibition of immune responses by tumor-secreted TGF-β and an increase in the number of regulatory T (Treg) cells in and around the solid tumor. Indeed, unlike DC therapy for solid tumors, cytotoxic T lymphocyte (CTL) responses induced by DC therapy inhibit tumor recurrence after surgery; CTL responses also limit tumor metastasis induced by additional tumor-challenge in RCC tumor-bearing mice. Here, we discuss the mechanisms underlying the poor efficacy of DC-based therapy for solid tumors and stress the need for new and improved DC immunotherapies and/or combination therapies with killer cells to treat resistant solid tumors.

Figure 1

Overview of immune cell-mediated anticancer immunity. DC immunotherapy inhibits the metastasis/recurrence of solid cancers, and killer cells such as CIK cells directly kill tumor cells; a combination of these cell-mediated therapeutics may prove very effective against many difficult-to-treat solid tumors. Treg, T regulatory cell; TGF-β, transforming growth factor-β; CIK, cytokine-induced killer cell.