Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns. An exhaustion severity metric was developed and integrated with high-dimensional phenotypes to define Tex cell clusters that were present in healthy subjects, common across chronic infection and cancer or enriched in either disease, linked to disease severity, and changed with HIV therapy. Combinatorial patterns of immunotherapy targets on different Tex cell clusters were also defined. This approach and associated datasets present a resource for investigating human Tex cell biology, with implications for immune monitoring and immunomodulation in chronic infections, autoimmunity, and cancer.

Bengsch, B., Ohtani, T., Khan, O., Setty, M., Manne, S., O'Brien, S., et al. (2018). Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. IMMUNITY, 48(5), 1029-1045.e5 [10.1016/j.immuni.2018.04.026].

Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells

Gherardini, Pier Federico;
2018-05-15

Abstract

Exhausted CD8 T (Tex) cells are immunotherapy targets in chronic infection and cancer, but a comprehensive assessment of Tex cell diversity in human disease is lacking. Here, we developed a transcriptomic- and epigenetic-guided mass cytometry approach to define core exhaustion-specific genes and disease-induced changes in Tex cells in HIV and human cancer. Single-cell proteomic profiling identified 9 distinct Tex cell clusters using phenotypic, functional, transcription factor, and inhibitory receptor co-expression patterns. An exhaustion severity metric was developed and integrated with high-dimensional phenotypes to define Tex cell clusters that were present in healthy subjects, common across chronic infection and cancer or enriched in either disease, linked to disease severity, and changed with HIV therapy. Combinatorial patterns of immunotherapy targets on different Tex cell clusters were also defined. This approach and associated datasets present a resource for investigating human Tex cell biology, with implications for immune monitoring and immunomodulation in chronic infections, autoimmunity, and cancer.
15-mag-2018
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
cancer immunology; CD8 T cell; chronic infection; CyTOF; HIV; immune checkpoint; lung cancer; mass cytometry; systems immunology; T cell exhaustion
Bengsch, B., Ohtani, T., Khan, O., Setty, M., Manne, S., O'Brien, S., et al. (2018). Epigenomic-Guided Mass Cytometry Profiling Reveals Disease-Specific Features of Exhausted CD8 T Cells. IMMUNITY, 48(5), 1029-1045.e5 [10.1016/j.immuni.2018.04.026].
Bengsch, B; Ohtani, T; Khan, O; Setty, M; Manne, S; O'Brien, S; Gherardini, Pf; Herati, Rs; Huang, Ac; Chang, K; Newell, Ew; Bovenschen, N; Pe'Er, D; Albelda, Sm; Wherry, Ej
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/312082
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