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. Author manuscript; available in PMC: 2018 May 1.
Published in final edited form as: Transplantation. 2017 May;101(5):894–895. doi: 10.1097/TP.0000000000001720

Figure 1.

Figure 1

Chronic antigen exposure installs enduring and irreversible epigenetic changes with a permanent exhaustion of antigen-specific CD8+ T cells that renders them only partially and temporarily responsive to PD-1 blockade. Following activation, effector T cells express permissive histone marks making their chromatin accessible for remodeling. As high levels of antigen persist, T cells upregulate PD-1 and repressive methylation that accumulates during chronic antigen exposure preventing exhausted cells from responding to checkpoint blockade. Thus, while blockade of PD-1 signaling can transiently restore T cell functionality, the underlying epigenetic landscape of exhausted T cells is not malleable and cannot be altered.

Adapted from Hazem E. Ghoneim, H. E., Zamora, A. E., Thomas, P. G., and Youngblood, B. A. Trends in Molecular Medicine, Vol. 22, Issue 12, p1000–1011