It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
TGF-β signaling is necessary for CD8+ T cell differentiation into tissue resident memory T cells (TRM). Although higher frequency of CD8+ TRM cells in the tumor microenvironment is associated with better prognosis, TGF-β−blockade typically improves rather than worsens outcomes. Here we show that in a mouse melanoma model, in the tumor-draining lymph nodes (TDLN) rather than in the tumors themselves, stem-like CD8+ T cells differentiate into TRMs in a TGF-β and tumor antigen dependent manner. Following vaccination against a melanoma-specific epitope, most tumour-specific CD8+ T cells are maintained in a stem-like state, but a proportion of cells lost TRM status and differentiate into CX3CR1+ effector CD8+ T cells in the TDLN, which are subsequently migrating into the tumours. Disruption of TGF-β signaling changes the dynamics of these developmental processes, with the net result of improving effector CD8+ T cell migration into the tumours. In summary, TDLN stem-like T cells transiently switch from a TGF-β-dependent TRM differentiation program to an anti-tumor migratory effector development upon vaccination, which transition can be facilitated by targeted TGF-β blockade.
TGF-β has been shown to regulate stem-like CD8 + T cell differentiation into tissue resident memory T cells in chronic infection. Here authors show that in tumour-bearing mice, a similar TGF-βdependent CD8 + T cell differentiation program is carried out in the draining lymph nodes, which impedes generation of anti-tumor migratory effector T cells upon future vaccination.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details



1 Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, Department of Microbiology, San Antonio, USA (GRID:grid.267309.9) (ISNI:0000 0001 0629 5880); Xiangya Hospital, Central South University, Department of Otolaryngology Head and Neck Surgery, Changsha, China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615); Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, China (GRID:grid.452223.0); Central South University, Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164)
2 Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, Department of Microbiology, San Antonio, USA (GRID:grid.267309.9) (ISNI:0000 0001 0629 5880)
3 Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, Department of Microbiology, San Antonio, USA (GRID:grid.267309.9) (ISNI:0000 0001 0629 5880); Central South University, Department of Hematology, The Third Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164)
4 Xiangya Hospital, Central South University, Department of Otolaryngology Head and Neck Surgery, Changsha, China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615); Sun Yat-Sen University Cancer Center, Department of Medical Imaging, Guangzhou, China (GRID:grid.488530.2) (ISNI:0000 0004 1803 6191)
5 Xiangya Hospital, Central South University, Department of Otolaryngology Head and Neck Surgery, Changsha, China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615)
6 Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, Department of Microbiology, San Antonio, USA (GRID:grid.267309.9) (ISNI:0000 0001 0629 5880); Central South University, Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Hunan Children’s Hospital, Department of Dermatology, Changsha, China (GRID:grid.440223.3) (ISNI:0000 0004 1772 5147)
7 Immunology and Molecular Genetics, Long School of Medicine, University of Texas Health Science Center at San Antonio, Department of Microbiology, San Antonio, USA (GRID:grid.267309.9) (ISNI:0000 0001 0629 5880); Dana-Farber Cancer Institute, Harvard Medical School, Department of Cancer Immunology and Virology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
8 Xiangya Hospital, Central South University, Department of Otolaryngology Head and Neck Surgery, Changsha, China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615); Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Hospital, Central South University, Changsha, China (GRID:grid.452223.0); Central South University, Clinical Research Center for Laryngopharyngeal and Voice Disorders in Hunan Province, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Central South University, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164)
9 Central South University, Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital, Changsha, China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Chinese Academy of Medical Sciences and Peking Union Medical College, Hospital for Skin Diseases (Institute of Dermatology), Nanjing, China (GRID:grid.506261.6) (ISNI:0000 0001 0706 7839)