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Cancer Res. 2016 Jul 1;76(13):3756-66. doi: 10.1158/0008-5472.CAN-15-3219.

Systemic DC Activation Modulates the Tumor Microenvironment and Shapes the Long-Lived Tumor-Specific Memory Mediated by CD8+ T Cells.

Author information

1
Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
2
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan.
3
Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
4
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
5
The Translational Research Center, The University of Tokyo Hospital, Tokyo, Japan.
6
Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Science, Yokohama, Kanagawa, Japan. shin-ichiro.fujii@riken.jp.

Abstract

Strategies to reprogram the tumor microenvironment are being explored to improve cancer immunotherapy. In one approach, we have targeted dendritic cells (DC) to improve their function with adjuvant vector cells (aAVC) that are engineered from NKT ligand-loaded CD1d(+) allogeneic cells transfected with tumor antigen mRNAs. Here, we report the finding that this approach also programs local immune responses by establishing tertiary lymphoid structures (TLS), which include expanded antigen-specific CD8(+) T-cell clones, mobilized DCs, and normalized tumor vasculature. aAVC therapy also expanded specific Vβ-expressing antitumor T-cell clones, leading to the formation of long-term memory T cells. When combined with PD-1 blockade, aAVC infusion triggered regression of poorly immunogenic tumor cells that did not respond to PD-1 blockade alone, as well as expansion of antigen-specific CD8(+) T-cell clones in the tumor. The findings of this study help to inform a next-generation platform for the generation of efficacious cancer vaccines. Cancer Res; 76(13); 3756-66.

PMID:
27371739
DOI:
10.1158/0008-5472.CAN-15-3219
[Indexed for MEDLINE]
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