Intratumoral Tcf1<sup>+</sup>PD-1<sup>+</sup>CD8<sup>+</sup> T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy.

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Version: Author's accepted manuscript
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_8DBCBF3E53B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Intratumoral Tcf1<sup>+</sup>PD-1<sup>+</sup>CD8<sup>+</sup> T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy.
Journal
Immunity
Author(s)
Siddiqui I., Schaeuble K., Chennupati V., Fuertes Marraco S.A., Calderon-Copete S., Pais Ferreira D., Carmona S.J., Scarpellino L., Gfeller D., Pradervand S., Luther S.A., Speiser D.E., Held W.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
15/01/2019
Peer-reviewed
Oui
Volume
50
Number
1
Pages
195-211.e10
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Checkpoint blockade mediates a proliferative response of tumor-infiltrating CD8 <sup>+</sup> T lymphocytes (TILs). The origin of this response has remained elusive because chronic activation promotes terminal differentiation or exhaustion of tumor-specific T cells. Here we identified a subset of tumor-reactive TILs bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD-1 and the transcription factor Tcf1. Tcf1 <sup>+</sup> PD-1 <sup>+</sup> TILs mediated the proliferative response to immunotherapy, generating both Tcf1 <sup>+</sup> PD-1 <sup>+</sup> and differentiated Tcf1 <sup>-</sup> PD-1 <sup>+</sup> cells. Ablation of Tcf1 <sup>+</sup> PD-1 <sup>+</sup> TILs restricted responses to immunotherapy. Tcf1 was not required for the generation of Tcf1 <sup>+</sup> PD-1 <sup>+</sup> TILs but was essential for the stem-like functions of these cells. Human TCF1 <sup>+</sup> PD-1 <sup>+</sup>  cells were detected among tumor-reactive CD8 <sup>+</sup> T cells in the blood of melanoma patients and among TILs of primary melanomas. Thus, immune checkpoint blockade relies not on reversal of T cell exhaustion programs, but on the proliferation of a stem-like TIL subset.
Keywords
Animals, Antibodies, Monoclonal/therapeutic use, CD8-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/immunology, Cell Differentiation, Cell Proliferation, Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors, Hepatocyte Nuclear Factor 1-alpha/genetics, Hepatocyte Nuclear Factor 1-alpha/metabolism, Humans, Immunotherapy, Lymphocytes, Tumor-Infiltrating/drug effects, Lymphocytes, Tumor-Infiltrating/immunology, Melanoma/immunology, Melanoma/therapy, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Stem Cells/immunology, T-Lymphocyte Subsets/immunology, T cell exhaustion, T cell factor 1, T cell reinvigoration, cancer immunotherapy, checkpoint blockade, memory-like T cells, stem-like T cells, therapeutic vaccination
Pubmed
Web of science
Create date
31/01/2019 9:14
Last modification date
05/02/2020 12:44
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