| Literature DB >> 32089832 |
José C Crispin1,2, George C Tsokos3,4.
Abstract
Clinical success attained in patients with cancer treated with checkpoint inhibitors has renewed the interest in the immune system and in particular in T cells as a therapeutic tool to eliminate tumors. Here, we discuss recent studies that evaluate the anti-tumor role of CD8 T cells and the mechanisms that interfere with this function. In particular, we review recent literature that has reported on the phenotype and transcriptome of tumor-infiltrating CD8 T cells and deciphered the mechanisms associated with failed tumor rejection. Copyright:Entities:
Keywords: CD8; PD-1; T cell; cancer; exhaustion
Year: 2020 PMID: 32089832 PMCID: PMC7001753 DOI: 10.12688/f1000research.21150.1
Source DB: PubMed Journal: F1000Res ISSN: 2046-1402
Figure 1. CD8 T-cell exhaustion in tumors determines prognosis and response to treatment.
CD8 T cells primed by tumor-derived antigens acquire effector functions and migrate to the tumor. The tumor microenvironment induces T-cell exhaustion through complex and not completely understood mechanisms that include repetitive antigenic stimulation, expression of co-inhibitory molecules (for example, PD-L1), abundance of inhibitory soluble molecules (for example, prostaglandin E2, adenosine, transforming growth factor beta, and interleukin-10), and regulatory T cells. Early exhausted T cells (Early stem-like Tex) express intermediate levels of PD-1 and the transcription factor TCF7 (TCF-1) that grants them self-renewing properties. Anti-PD-1 therapy is able to reinvigorate this population and, in some tumors, its abundance predicts good response to PD-1 blockade. Terminally exhausted T cells (Terminal Tex) no longer express TCF7 and bear high levels of PD-1. These cells fail to respond to PD-1 blockade but may regain effector capacities when other molecules (for example, TIM3 and CD39) are inhibited. ICI, immune checkpoint inhibitor.