Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice

Chengwen Liu, Yanyan Lou, Gregory Lizée, Hong Qin, Shujuan Liu, Brian Rabinovich, Grace J. Kim, Yi Hong Wang, Yang Ye, Andrew G. Sikora, Willem W. Overwijk, Yong Jun Liu, Gang Wang, Patrick Hwu

Research output: Contribution to journalArticlepeer-review

222 Scopus citations

Abstract

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-? production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)1165-1175
Number of pages11
JournalJournal of Clinical Investigation
Volume118
Issue number3
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice'. Together they form a unique fingerprint.

Cite this