Journal
SEMINARS IN IMMUNOLOGY
Volume 52, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.smim.2021.101480
Keywords
PD-1 pathway; Cancer immunotherapy; Immune regulation; Neoadjuvant; T cell exhaustion
Categories
Funding
- National Institutes of Health [P01 AI56299, P01AI039671, P01 AI108545, NIH P50 CA206963, P50CA101942, P01AI056299, R01 CA234018]
- ASCO Young Investigator Award
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The PD-1 pathway is essential in immune regulation, playing diverse roles beyond maintaining T cell exhaustion in chronic infection and cancer. PD-1 blockade impacts various T cell differentiation states, regulates Treg cells, NK cells, and ILCs, and has potential in early-stage cancer treatment.
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-Ll/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.
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