| Autor: |
Silvia A. Fuertes Marraco, Leonardo Scarpellino, Vijaykumar Chennupati, Sylvain Pradervand, Daniela Pais Ferreira, Karin Schaeuble, Imran Siddiqui, Werner Held, Sanjiv A. Luther, Sandra Calderon-Copete, Santiago J. Carmona, Daniel E. Speiser, David Gfeller |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Immunity, vol. 50, no. 1, pp. 195-211.e10 |
| ISSN: |
1074-7613 |
| DOI: |
10.1016/j.immuni.2018.12.021 |
| Popis: |
Checkpoint blockade mediates a proliferative response of tumor-infiltrating CD8 + 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 + PD-1 + TILs mediated the proliferative response to immunotherapy, generating both Tcf1 + PD-1 + and differentiated Tcf1 - PD-1 + cells. Ablation of Tcf1 + PD-1 + TILs restricted responses to immunotherapy. Tcf1 was not required for the generation of Tcf1 + PD-1 + TILs but was essential for the stem-like functions of these cells. Human TCF1 + PD-1 + cells were detected among tumor-reactive CD8 + 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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