Tumors Suppress In Situ Proliferation of Cytotoxic T Cells by Promoting Differentiation of Gr-1+ Conventional Dendritic Cells through IL-6

Abstract

Cancers are often accompanied by inflammation, which can promote tumor growth, invasion, and metastases. We show that the tumor microenvironment induces the development of a Gr-1+ conventional dendritic cell (cDC) subpopulation that is functionally defective. Gr-1+cDCs differentiated from recruited immediate precursors of cDCs, a process supported by the inflammatory cytokine milieu in tumors. Inhibition of Gr-1+cDC differentiation enhanced intratumor expansion of cytotoxic CD8+ T cells (CTLs), resulting in suppression of tumor growth. Diphtheria toxin treatment of CD11c–diphtheria toxin receptor chimeras revealed the importance of intratumor cDCs in stimulating CTL proliferation in situ. Our study demonstrates a key role of intratumor cDCs in determining antitumor CTL responses and suggests that they may be an appropriate target for tumor immunotherapy.