Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

• Published in: Immunity (Cambridge, Mass.) Vol. 52; no. 5; pp. 825 - 841.e8
• Main Authors: Beltra, Jean-Christophe, Manne, Sasikanth, Abdel-Hakeem, Mohamed S., Kurachi, Makoto, Giles, Josephine R., Chen, Zeyu, Casella, Valentina, Ngiow, Shin Foong, Khan, Omar, Huang, Yinghui Jane, Yan, Patrick, Nzingha, Kito, Xu, Wei, Amaravadi, Ravi K., Xu, Xiaowei, Karakousis, Giorgos C., Mitchell, Tara C., Schuchter, Lynn M., Huang, Alexander C., Wherry, E. John
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.05.2020; Elsevier Limited
• Subjects: Animals; B7-H1 Antigen - genetics; B7-H1 Antigen - immunology; Biological effects; Biology; Cancer; Cancer immunotherapy; CD8; CD8 antigen; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell cycle; Cells, Cultured; chronic infection; Developmental biology; Epigenesis, Genetic - genetics; Epigenesis, Genetic - immunology; Epigenetics; Exhaustion; Hepatocyte nuclear factor 1; Hepatocyte Nuclear Factor 1-alpha - genetics; Hepatocyte Nuclear Factor 1-alpha - immunology; Homeodomain Proteins - genetics; Homeodomain Proteins - immunology; Humans; Immunotherapy; Immunotherapy - methods; Infections; Lymphocytes; Lymphocytes T; Mice, Inbred C57BL; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - therapy; PD-1 blockade; PD-L1 protein; Population; T cell exhaustion lineage; T cell receptors; T-bet; T-Box Domain Proteins - genetics; T-Box Domain Proteins - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; TCF1; Tox; Transcription; Transcription, Genetic - genetics; Transcription, Genetic - immunology; Tumors; Viral infections; T cell exhaustion lineage; chronic infection; CD8; cancer immunotherapy; exhaustion; PD-1 blockade; Tox; TCF1; T-bet; epigenetics

CD8+ T cell exhaustion is a major barrier to current anti-cancer immunotherapies. Despite this, the developmental biology of exhausted CD8+ T cells (Tex) remains poorly defined, restraining improvement of strategies aimed at “re-invigorating” Tex cells. Here, we defined a four-cell-stage development...