Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy

By S. Spranger, D. Dai, B. Horton, T. Gajewski. Cancer Cell, 2017

1,222 citations recorded by the source corpus.

Summary Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune-resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to absence of CXCL9/10, which we found to be produced by CD103+ dendritic cells (DC) in T cell-inflamed tumors. Our data indicate that lack of CD103+ DC within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/8f00fd22736abf3990e0e553ad171da8a1281577

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Citations in the corpus

Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. (2019, background): “cDCs were previously reported to cross-present antigens to CD8+ T cells, and their presence is correlated with response to checkpoint inhibitors in patients (33, 34).”
Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I (2020, positive): “We also find that mice deficient for CD103 + dendritic cells (DCs; Batf3 −/− ) 21 , which play pivotal roles in CD8 + T-cell priming 22 and recruitment into tumours 20,23 , showed almost complete loss of tumour-infiltrating CD8 + T cells (Fig.”
Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti–PD-1 treatment (2018, background): “Tumor cells, as well as CD103 DC, recently shown to attract T cells into tumors through the production of CXCR3 ligands, are good candidates (29).”
NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control (2018, background): “, CXCL9 and CXCL10) that could attract NK cells via CXCR3 (Spranger et al., 2017; Wendel et al., 2008).”
Tumor cell-intrinsic factors underlie heterogeneity of immune cell infiltration and response to immunotherapy (2018, positive): “, 2015; 2017), but not via the CXCR3 pathway reported for melanoma (Spranger et al., 2017).”
Cold Tumors: A Therapeutic Challenge for Immunotherapy (2019, background): “Moreover, DC1s are a source of CXCL-9/10 and their absence lead to a reduced production of these chemokines (20).”