Dendritic Cells and Cancer Immunity. Issue 12 (December 2016)

• Record Type: Journal Article
• Authors: Gardner, Alycia; Ruffell, Brian
• Is Part Of: Trends in immunology. Volume 37:Issue 12(2016)
• Page Start: 855
• Page End: 865
• Publication Date: 2016-12
• Subjects: antigen presentation -- cancer -- dendritic cells -- immunotherapy -- vaccination -- tumor microenvironment; Immunology -- Periodicals; 571.96
• DOI: 10.1016/j.it.2016.09.006
• Languages: English
• ISSNs: 1471-4906

Abstract

Abstract : Dendritic cells (DCs) are central regulators of the adaptive immune response, and as such are necessary for T-cell-mediated cancer immunity. In particular, antitumoral responses depend on a specialized subset of conventional DCs that transport tumor antigens to draining lymph nodes and cross-present antigen to activate cytotoxic T lymphocytes. DC maturation is necessary to provide costimulatory signals to T cells, but while DC maturation occurs within tumors, it is often insufficient to induce potent immunity, particularly in light of suppressive mechanisms within tumors. Bypassing suppressive pathways or directly activating DCs can unleash a T-cell response, and although clinical efficacy has proven elusive, therapeutic targeting of DCs continues to hold translational potential in combinatorial approaches. Trends: Conventional dendritic cells type 1 (cDC1s) are necessary for inducing antitumor T-cell responses. This appears to trace to the ability of migratory cDC1 to deliver tumor antigen and cross-present to CD8 + T cells. Spontaneous antitumor immunity is dependent on activation of cDCs by type I interferon (IFN). Expression of type I IFNs is induced in myeloid cells via recognition of cytosolic DNA and activation of the stimulator of IFN genes complex (STING) pathway. Intratumoral cDC1s are capable of restimulating CD8 + T cells and may be important within tumors for antigen presentation and/or cytokine expression. The next generation of vaccines consisting of patient-specific neoantigens or attenuated pathogens may demonstrate single-agent efficacy or find utility in combination with checkpoint blockade.