Emerging concepts in PD-1 checkpoint biology

•The PD-1 pathway plays multifaceted roles in regulating immune responses.•PD-1 can modulate effector and memory T cells, Treg cells, NK cells, and ILCs.•PD-1 regulates anti-tumor T cells in the draining lymph node as well as in the tumor.•Timing of PD-1 inhibition may be important for durable anti-...

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Vydáno v:	Seminars in immunology Ročník 52; s. 101480
Hlavní autoři:	Pauken, Kristen E., Torchia, James A., Chaudhri, Apoorvi, Sharpe, Arlene H., Freeman, Gordon J.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Ltd 01.02.2021
Témata:	Cancer immunotherapy Humans Immune Checkpoint Inhibitors - therapeutic use Immune regulation Killer Cells, Natural Lymphocyte Activation Neoadjuvant Neoplasms - therapy PD-1 pathway Programmed Cell Death 1 Receptor - antagonists & inhibitors T cell exhaustion ILC TCR FDA LCMV MSIhi T cell exhaustion MHC Neoadjuvant RGMb Cancer immunotherapy TNF ORR IFN GBM LAG-3 MMRd PD-L1 PD-L2 INMC CTLA-4 TIM-3 PD-1 pathway pCR CD NSCLC TCF-1 MMPr Treg TMB Immune regulation RCC APC CAR TIL irAE PD-1 NK HPD DC
ISSN:	1044-5323, 1096-3618, 1096-3618
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Popis
Shrnutí:	•The PD-1 pathway plays multifaceted roles in regulating immune responses.•PD-1 can modulate effector and memory T cells, Treg cells, NK cells, and ILCs.•PD-1 regulates anti-tumor T cells in the draining lymph node as well as in the tumor.•Timing of PD-1 inhibition may be important for durable anti-tumor immunity.•PD-L1/B7-1 and PD-L2/RGMb/neogenin interactions broaden the impact of the pathway. The PD-1 pathway is a cornerstone in immune regulation. While the PD-1 pathway has received considerable attention for its role in contributing to the maintenance of T cell exhaustion in chronic infection and cancer, the PD-1 pathway plays diverse roles in regulating host immunity beyond T cell exhaustion. Here, we discuss emerging concepts in the PD-1 pathway, including (1) the impact of PD-1 inhibitors on diverse T cell differentiation states including effector and memory T cell development during acute infection, as well as T cell exhaustion during chronic infection and cancer, (2) the role of PD-1 in regulating Treg cells, NK cells, and ILCs, and (3) the functions of PD-L1/B7-1 and PD-L2/RGMb/neogenin interactions. We then discuss the emerging use of neoadjuvant PD-1 blockade in the treatment of early-stage cancers and how the timing of PD-1 blockade may improve clinical outcomes. The diverse binding partners of PD-1 and its associated ligands, broad expression patterns of the receptors and ligands, differential impact of PD-1 modulation on cells depending on location and state of differentiation, and timing of PD-1 blockade add additional layers of complexity to the PD-1 pathway, and are important considerations for improving the efficacy and safety of PD-1 pathway therapeutics.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23
ISSN:	1044-5323 1096-3618 1096-3618
DOI:	10.1016/j.smim.2021.101480