Effect of Lymphodepletion on Donor T Cells and the Role of Recipient Cells Persisting after Cytotoxic Treatments in Cancer Immunotherapies.

The effectiveness of lymphodepletion in antitumor immunity has been well established. Although recent studies have elucidated some of the broad mechanisms underlying the augmentation of antitumor immunity by lymphodepletion, such as increased availability of cytokines due to the elimination of cellular elements and improvement in tumor antigen presentation, the precise mechanisms remain unclear. Previous studies have focused on the enhancement of the functions of transferred antitumor CD8+ T cells after lymphodepletion. In this review, we discuss the important role of other immune cells in the effectiveness of lymphodepletion. Recent studies have demonstrated that lymphodepletion enhances not only transferred tumor-specific CD8+ T cells but also tumor-specific CD4+ T cells and polyclonal naïve T cells. Moreover, recipient immune cells, including CD8+ T cells, regulatory T cells, dendritic cells, and macrophages, are involved in the augmentation of antitumor effects by lymphodepletion. These host cells can survive lymphodepletive therapies and play a role in the development of antitumor immunity after lymphodepletion. Improvements in the understanding of lymphodepletion allow us to design effective cancer immunotherapy.