| First Author | Nesbeth Y | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 15 | Pages | 6331-8 |
| PubMed ID | 19602595 | Mgi Jnum | J:150956 |
| Mgi Id | MGI:3852586 | Doi | 10.1158/0008-5472.CAN-08-4329 |
| Citation | Nesbeth Y, et al. (2009) CCL5-mediated endogenous antitumor immunity elicited by adoptively transferred lymphocytes and dendritic cell depletion. Cancer Res 69(15):6331-8 |
| abstractText | 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. |
