| First Author | Diao J | Year | 2018 |
| Journal | J Immunol | Volume | 201 |
| Issue | 4 | Pages | 1306-1314 |
| PubMed ID | 29997124 | Mgi Jnum | J:264508 |
| Mgi Id | MGI:6195476 | Doi | 10.4049/jimmunol.1701514 |
| Citation | Diao J, et al. (2018) Tumor Dendritic Cells (DCs) Derived from Precursors of Conventional DCs Are Dispensable for Intratumor CTL Responses. J Immunol 201(4):1306-1314 |
| abstractText | The success of adoptive CTL therapy for cancer depends on interactions between tumor-infiltrating CTLs and cancer cells as well as other cells and molecules in the tumor microenvironment. Tumor dendritic cells (DCs) comprise several subsets: CD103(+)CD11b(-) DC1 and CD11b(+)CD64(-) DC2, which originate from circulating precursors of conventional DCs, and CD11b(+)CD64(+) DC3, which arise from monocytes. It remains controversial which of these subset(s) promotes intratumor CTL proliferation, expansion, and function. To address this issue, we used the Zbtb46-DTR-transgenic mouse model to selectively deplete DC1 and DC2 from tumors and lymphoid tissues. Wild-type and Zbtb46-DTR bone marrow chimeras were inoculated with B16 melanoma cells that express OVA and were treated with OT-1 CTLs. We found that depletion of DCs derived from precursors of conventional DCs in Zbtb46-DTR bone marrow chimeras abolished CTL proliferation and expansion in tumor-draining lymph nodes. By contrast, intratumor CTL accumulation, proliferation, and IFN-gamma expression were unaffected by their absence. We found that adoptive cell therapy increases the frequency of monocyte-derived tumor DC3, which possess the capacity to cross-present tumor Ags and induce CTL proliferation. Our findings support the specialized roles of different DC subsets in the regulation of antitumor CTL responses. |
