TY - JOUR
T1 - Quantifying pd-l1 expression to monitor immune checkpoint therapy
T2 - Opportunities and challenges
AU - Nimmagadda, Sridhar
N1 - Funding Information:
This research was funded by Allegheny Health Network-Johns Hopkins Cancer Research Fund (SN), National Institutes of Health: NIH 1R01CA236616 and NIH P41EB024495. This work was also supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Breast Cancer Research Program, under Award No. W81XWH-16-1-0323. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
PY - 2020/11
Y1 - 2020/11
N2 - Therapeutics targeting programmed death ligand 1 (PD-L1) protein and its receptor PD-1 are now dominant players in restoring anti-tumor immune responses. PD-L1 detection by immunohistochemistry (IHC) is emerging as a reproducible biomarker for guiding patient stratification for those therapies in some cancers. However, PD-L1 expression in the tumor microenvironment is highly complex. It is upregulated by aberrant genetic alterations, and is highly regulated at the transcriptional, posttranscriptional, and protein levels. Thus, PD-L1 IHC is inadequate to fully understand the relevance of PD-L1 levels in the whole body and their dynamics to improve therapeutic outcomes. Imaging technologies could potentially assist in meeting that need. Early clinical investigations show promising results in quantifying PD-L1 expression in the whole body by positron emission tomography (PET). Within this context, this review summarizes advancements in regulation of PD-L1 expression and imaging agents, and in PD-L1 PET for drug development, and discusses opportunities and challenges presented by these innovations for guiding immune checkpoint therapy (ICT).
AB - Therapeutics targeting programmed death ligand 1 (PD-L1) protein and its receptor PD-1 are now dominant players in restoring anti-tumor immune responses. PD-L1 detection by immunohistochemistry (IHC) is emerging as a reproducible biomarker for guiding patient stratification for those therapies in some cancers. However, PD-L1 expression in the tumor microenvironment is highly complex. It is upregulated by aberrant genetic alterations, and is highly regulated at the transcriptional, posttranscriptional, and protein levels. Thus, PD-L1 IHC is inadequate to fully understand the relevance of PD-L1 levels in the whole body and their dynamics to improve therapeutic outcomes. Imaging technologies could potentially assist in meeting that need. Early clinical investigations show promising results in quantifying PD-L1 expression in the whole body by positron emission tomography (PET). Within this context, this review summarizes advancements in regulation of PD-L1 expression and imaging agents, and in PD-L1 PET for drug development, and discusses opportunities and challenges presented by these innovations for guiding immune checkpoint therapy (ICT).
KW - Immune checkpoints
KW - Immuno-Oncology
KW - Interferon-γ signaling
KW - PET imaging
KW - Tumor microenvironment
KW - Tumor mutational burden
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U2 - 10.3390/cancers12113173
DO - 10.3390/cancers12113173
M3 - Review article
C2 - 33137949
AN - SCOPUS:85094616563
VL - 12
SP - 1
EP - 26
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 11
M1 - 3173
ER -