CD8+Foxp3+ tumor infiltrating lymphocytes accumulate in the context of an effective anti-tumor response†
Corresponding Author
Dung T. Le
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
D. L. and B. L. contributed equally to this work
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, 1650 Orleans St., Rm 407, Baltimore, MD 21231, USASearch for more papers by this authorBrian H. Ladle
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTimothy Lee
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
D. L. and B. L. contributed equally to this work
Search for more papers by this authorVivian Weiss
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorXiaosai Yao
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorAshley Leubner
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTodd D. Armstrong
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorElizabeth M. Jaffee
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorCorresponding Author
Dung T. Le
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
D. L. and B. L. contributed equally to this work
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine, 1650 Orleans St., Rm 407, Baltimore, MD 21231, USASearch for more papers by this authorBrian H. Ladle
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTimothy Lee
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
D. L. and B. L. contributed equally to this work
Search for more papers by this authorVivian Weiss
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorXiaosai Yao
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorAshley Leubner
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorTodd D. Armstrong
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorElizabeth M. Jaffee
The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Immunology, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
Search for more papers by this authorThrough a licensing agreement by Johns Hopkins University to Bio Sante, Johns Hopkins University has the potential to receive royalties in the future.
Abstract
The composition of tumor infiltrating lymphocytes (TIL) is heterogeneous. In addition, the ratio of various subpopulations in the tumor microenvironment is highly dependent on the nature of the host's immune response. Here, we characterize Foxp3-expressing CD8+ T cells in the tumor that demonstrate effector function and accumulate in the context of an effective anti-tumor response. CD8+Foxp3+ T cells are induced in TIL in regressing tumors of FVB/N mice treated with a GM-CSF secreting HER-2/neu targeted whole cell vaccine. Foxp3 expression in tumor antigen-specific CD8 T cells is restricted to the tumor microenvironment and influenced by cues in the tumor. Interestingly, Foxp3+ and Foxp3− CD8+ T cells have similar IFN-γ production and antigen-specific degranulation after stimulation with RNEU420–429, the immunodominant HER-2/neu (neu) epitope in this model. Adoptive transfer studies, using RNEU(420–429)-specific effector T cells into neu-N mice (a model that results in immune tolerance to neu), confirm that CD8+Foxp3+ T cells are present in tumors only if there is an existing pool of tumor-rejecting effector T cells. CD8+Foxp3+ TILs mark the presence of tumor-rejecting antigen-specific T cells and their accumulation serves as a marker for an effective T cell response.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
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| IJC_25693_sm_suppfig-S1.tif52.4 KB | Supporting Figure 1 |
| IJC_25693_sm_suppfig-S2.tif98.9 KB | Supporting Figure 2 |
| IJC_25693_sm_suppfig-S3.tif5 KB | Supporting Figure 3 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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