title: 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.
authors: Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario M5G 2N2, Canada.
authors: Jun
authors: J
authors: Diao
authors: Jun
authors: J
authors: Zhao
authors: Erin
authors: E
authors: Winter
authors: Mark S
authors: MS
authors: Cattral
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015850:Interleukin-6 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology*
chemical_list: C503133:Gr-1 protein, mouse; D015850:Interleukin-6; D019707:Receptors, Chemokine