Critical Role for CD103+/CD141+ Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma

By Edward W. Roberts, Miranda L. Broz, M. Binnewies, M. Headley, Amanda E. Nelson, D. Wolf, T. Kaisho, D. Bogunovic, N. Bhardwaj, M. Krummel. Cancer Cell, 2016

890 citations recorded by the source corpus.

SUMMARY 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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/b690332c5196a9f40d6d3b55d84c50bfee4a9b23

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In Immunology

1. Lisa M. Coussens
2. Erik Sahai
3. D. Pardoll
4. Zena Werb
5. Janis Taube
6. S. Spranger
7. S. Topalian
8. B. Ruffell

In Oncology

1. Lisa M. Coussens
2. Zena Werb
3. Erik Sahai
4. D. Pardoll
5. Janis Taube
6. S. Topalian
7. B. Ruffell
8. S. Spranger

Citations in the corpus

• Neoadjuvant checkpoint blockade for cancer immunotherapy (2020, background): “By contrast, there was no evidence for tumor antigen–carryingmacrophages in lymph nodes (39).”
• Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy (2018, positive): “Cross-Presenting Dendritic Cells and CXCR3 Are Necessary for CD8 T Cell Infiltration Cross-presenting dendritic cells (DCs) play a critical role in presenting tumor antigens to CD8 T cells (Roberts et al., 2016).”
• Dendritic Cells and Cancer Immunity (2016, methodology): “Roberts EW, et al. Critical Role for CD103(+)/CD141(+) Dendritic Cells Bearing CCR7 for Tumor Antigen Trafficking and Priming of T Cell Immunity in Melanoma.”
• Roles of the immune system in cancer: from tumor initiation to metastatic progression (2018, background): “CD103 + DCs have critical roles in tumor antigen presentation in transgenic and xenograft mouse models of melanoma and breast and cervical cancer (Broz et al. 2014; Moynihan et al. 2016; Roberts et al. 2016).”
• Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy (2017, methodology): “to depend upon Batf3-driven DCs, and rejection of immunogenic tumors is ablated in Batf3 / mice (Broz et al., 2014; Edelson et al., 2010; Engelhardt et al., 2012; Fuertes et al., 2011; Roberts et al., 2016).”
• Single cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species (2019, background): “CCR7 expression may enable mDC3 to migrate to draining lymph nodes (Roberts et al., 2016) but some of these cells can remain within tumors (Garris et al.”
• Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment (2019, background): “Accordingly, a study assessing gene-signatures also associated high intra-tumoral levels of CD141 DCs with better overall survival in melanoma patients (155).”