CCL5-mediated endogenous antitumor immunity elicited by adoptively transferred lymphocytes and dendritic cell depletion.
Journal Article (Journal Article)
Adoptive transfer of antitumor T cells is a promisingly effective therapy for various cancers, but its effect on endogenous antitumor immune mechanisms remains largely unknown. Here, we show that the administration of naive T cells de novo primed for only 7 days against tumor antigens resulted in the durable rejection of otherwise lethal ovarian cancers when coupled with the depletion of tumor-associated immunosuppressive dendritic cells (DC). Therapeutic activity required tumor antigen specificity and perforin expression by the adoptively transferred T cells, but not IFN-gamma production. Importantly, these shortly primed T cells secreted large amounts of CCL5, which was required for their therapeutic benefit. Accordingly, transferred T cells recruited CCR5(+) DCs into the tumor, where they showed distinct immunostimulatory attributes. Activated CCR5(+) host T cells with antitumor activity also accumulated at tumor locations, and endogenous tumor-specific memory T cells remained elevated after the disappearance of transferred lymphocytes. Therefore, persistent, long-lived antitumor immunity was triggered by the administration of ex vivo activated T cells, but was directly mediated by immune cells of host origin. Our data unveil a CCL5-dependent mechanism of awakening endogenous antitumor immunity triggered by ex vivo expanded T cells, which is augmented by tumor-specific targeting of the cancer microenvironment.
- Nesbeth, Y; Scarlett, U; Cubillos-Ruiz, J; Martinez, D; Engle, X; Turk, M-J; Conejo-Garcia, JR
- August 1, 2009
Volume / Issue
- 69 / 15
Start / End Page
- 6331 - 6338
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States