Journal
TRENDS IN IMMUNOLOGY
Volume 41, Issue 8, Pages 665-675Publisher
CELL PRESS
DOI: 10.1016/j.it.2020.06.008
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Funding
- National Institutes of Health [1R01AI114442]
- Loan Repayment Program(LRP)
- Immune Tolerance Network
- American Lebanese Syrian Associated Charities (ALSAC)
- Assisi foundation
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The full potential of T cell-based immunotherapies remains limited by a vari-ety of T cell extrinsic and intrinsic immunosuppressive mechanisms that can become imprinted to stably reduce the antitumor ability of T cells. Here, we discuss recent insights into memory CD8(+)T cell differentiation and exhaustion and the association of these differentiation states with clinical outcomes during im-mune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapeutic modalities. We consider the barriers limiting immunotherapy with a focus on epigenetic regulation impeding efficacy of adoptively transferred T cells and other approaches that augment T cell responses such as immune checkpoint blockade. Furthermore, we outline conceptual and technical breakthroughs that can be applied to existing therapeutic approaches and to the development of novel cutting-edge strategies.
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