caa a22 4500 555159590 CHVBK 20200720043721.0 cr unu---uuuuu 190202e20190115xx s 000 0 eng 10.1016/j.immuni.2018.12.021 doi (SERVAL)BIB_8DBCBF3E53B5 30635237 pmid 000455661600020 isiid Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy [Elektronische Daten] [I. Siddiqui, K. Schaeuble, V. Chennupati, S.A. Fuertes Marraco, S. Calderon-Copete, D. Pais Ferreira, S.J. Carmona, L. Scarpellino, D. Gfeller, S. Pradervand, S.A. Luther, D.E. Speiser, W. Held] 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. Siddiqui I. aut Schaeuble K. aut Chennupati V. aut Fuertes Marraco S.A. aut Calderon-Copete S. aut Pais Ferreira D. aut Carmona S.J. aut Scarpellino L. aut Gfeller D. aut Pradervand S. aut Luther S.A. aut Speiser D.E. aut Held W. aut Immunity 50/1(2019-01-15), 195-211.e10 50:1<195-211.e10 2019 50 BK010053 XK010053 XK010000 1 article serval SERVAL SERVAL SERVAL article SERVAL 700 1- Siddiqui I. aut SERVAL 700 1- Schaeuble K. aut SERVAL 700 1- Chennupati V. aut SERVAL 700 1- Fuertes Marraco S.A. aut SERVAL 700 1- Calderon-Copete S. aut SERVAL 700 1- Pais Ferreira D. aut SERVAL 700 1- Carmona S.J. aut SERVAL 700 1- Scarpellino L. aut SERVAL 700 1- Gfeller D. aut SERVAL 700 1- Pradervand S. aut SERVAL 700 1- Luther S.A. aut SERVAL 700 1- Speiser D.E. aut SERVAL 700 1- Held W. aut SERVAL 773 0- Immunity 50/1(2019-01-15), 195-211.e10 50:1<195-211.e10 2019 50