학술논문

Critical Role for CD103+/CD141+ Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma
Document Type
article
Source
Cancer Cell. 30(2)
Subject
Biomedical and Clinical Sciences
Oncology and Carcinogenesis
Immunology
Immunization
Cancer
Inflammatory and immune system
Animals
Antigen Presentation
Antigens
CD
Antigens
Neoplasm
Antigens
Surface
CD8-Positive T-Lymphocytes
Cell Movement
Dendritic Cells
Humans
Integrin alpha Chains
Lymph Nodes
Melanoma
Melanoma
Experimental
Mice
Mice
Inbred C57BL
Mice
Transgenic
Receptors
CCR7
Thrombomodulin
2-photon imaging
anti-tumor T cell priming
antigen presentation
antigen trafficking
dendritic cells
draining lymph node
melanoma
tumor
tumor immune response
Neurosciences
Oncology & Carcinogenesis
Biochemistry and cell biology
Oncology and carcinogenesis
Language
Abstract
Intratumoral dendritic cells (DC) bearing CD103 in mice or CD141 in humans drive intratumoral CD8(+) T cell activation. Using multiple strategies, we identified a critical role for these DC in trafficking tumor antigen to lymph nodes (LN), resulting in both direct CD8(+) T cell stimulation and antigen hand-off to resident myeloid cells. These effects all required CCR7. Live imaging demonstrated direct presentation to T cells in LN, and CCR7 loss specifically in these cells resulted in defective LN T cell priming and increased tumor outgrowth. CCR7 expression levels in human tumors correlate with signatures of CD141(+) DC, intratumoral T cells, and better clinical outcomes. This work identifies an ongoing pathway to T cell priming, which should be harnessed for tumor therapies.