Tumor-Residing Batf3 Dendritic Cells Are Required for Effector T Cell Trafficking and Adoptive T Cell Therapy

Publication date: 8 May 2017
Source:Cancer Cell, Volume 31, Issue 5
Author(s): Stefani Spranger, Daisy Dai, Brendan Horton, Thomas F. Gajewski
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 the absence of CXCL9/10, which we found to be produced by CD103⁺ dendritic cells (DCs) in T cell-inflamed tumors. Our data indicate that lack of CD103⁺ DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape.

Graphical abstract

Teaser

Spranger et al. show that effector T cells from adoptive T cell transfer fail to traffic to a non-T cell-inflamed melanoma model due to lack of CXCL9/10 produced by Batf3-driven dendritic cells that are present in inflamed tumors but absent in non-inflamed tumors. Human melanomas appear to have similar regulation.


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