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Programmed death-ligand 1 (view source)
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'''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is a protein with an important role in immune system regulation and [[cancer]]. | [[Image:PD-L1_positive_lung_adenocarcinoma_--_intermed_mag.jpg|right|thumb|[[Micrograph]] showing a PD-L1 positive non-small cell lung carcinoma (NSCLC). PD-L1 [[immunostain]] (22C3). (WC)]] | ||
'''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is a protein with an important role in immune system regulation and [[cancer]]. | |||
[[Image:PD-L1 negative lung adenocarcinoma -- high mag.jpg|right|thumb|[[Micrograph]] showing a PD-L1 negative [[NSCLC]]. PD-L1 immunostain (22C3). (WC)]] | |||
Normally, PD-L1 on cells binds with [[programmed cell death 1]] on the T lymphocytes.<ref name=pmid22658126/> | Normally, PD-L1 on cells binds with [[programmed cell death 1]] on the T lymphocytes.<ref name=pmid22658126/> | ||
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==General== | ==General== | ||
[[Image:PD-L1_positive_lung_adenocarcinoma_in_lymph_node_--_intermed_mag.jpg|thumb|right|PD-L1 positive lung adenocarcinoma in a lymph node. 22C3 PD-L1 immunostain. (WC)]] | |||
*In theory, positive PD-L1 [[IHC|immunostaining]] predicts response to anti-PD-L1 drugs.<ref name=pmid26970723/> | *In theory, positive PD-L1 [[IHC|immunostaining]] predicts response to anti-PD-L1 drugs.<ref name=pmid26970723/> | ||
**Carcinoma cell is considered "PD-L1 positive" if the cell membrane is partially or completely stained. <ref name="pmid27389313">{{ | **Carcinoma cell is considered "PD-L1 positive" if the cell membrane is partially or completely stained.<ref name="pmid27389313">{{Cite journal | last1 = Scheel | first1 = AH. | last2 = Dietel | first2 = M. | last3 = Heukamp | first3 = LC. | last4 = Jöhrens | first4 = K. | last5 = Kirchner | first5 = T. | last6 = Reu | first6 = S. | last7 = Rüschoff | first7 = J. | last8 = Schildhaus | first8 = HU. | last9 = Schirmacher | first9 = P. | title = Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. | journal = Mod Pathol | volume = 29 | issue = 10 | pages = 1165-72 | month = Oct | year = 2016 | doi = 10.1038/modpathol.2016.117 | PMID = 27389313 }}</ref> | ||
*It is, however, more complex than that. Some tumour types are invariably positive, e.g. classical Hodgkin lymphoma, so testing is unhelpful. In contrast, tumors such as malignant melanoma respond regardless of PD-L1 immunoexpression. | *It is, however, more complex than that. Some tumour types are invariably positive, e.g. classical Hodgkin lymphoma, so testing is unhelpful. In contrast, tumors such as malignant melanoma respond regardless of PD-L1 immunoexpression. | ||
*The plethora of companion diagnostics developed for each PD-1/ PD-L1 inhibitor has created challenges, as these assays include different IHC antibody clones, staining protocols and platforms, scoring systems, and cutoffs for defining positivity. | *The plethora of companion diagnostics developed for each PD-1/ PD-L1 inhibitor has created challenges, as these assays include different IHC antibody clones, staining protocols and platforms, scoring systems, and cutoffs for defining positivity. | ||
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| [[PD-L1]] (CD274), PD-L2 (CD273) | | [[PD-L1]] (CD274), PD-L2 (CD273) | ||
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===Adequacy of PD-L1=== | |||
*100 cells or more.<ref name=pmid31097091>{{cite journal |authors=Wang H, Agulnik J, Kasymjanova G, Fiset PO, Camilleri-Broet S, Redpath M, Cohen V, Small D, Pepe C, Sakr L, Spatz A |title=The metastatic site does not influence PD-L1 expression in advanced non-small cell lung carcinoma |journal=Lung Cancer |volume=132 |issue= |pages=36–38 |date=June 2019 |pmid=31097091 |doi=10.1016/j.lungcan.2019.04.009 |url=}}</ref> | |||
==Prognosis== | ==Prognosis== | ||
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==Drugs - Immune checkpoint inhibitors== | ==Drugs - Immune checkpoint inhibitors== | ||
*PD-1 inhibitors: | *PD-1 inhibitors: | ||
**Nivolumab | **Nivolumab (''Opdivo'', Bristol-Myers Squibb). | ||
**Pembrolizumab | **Pembrolizumab (''Keytruda'', Merck). | ||
*PD-L1 inhibitors: | *PD-L1 inhibitors: | ||
**Atezolizumab.<ref name=pmid26970723>{{Cite journal | last1 = Fehrenbacher | first1 = L. | last2 = Spira | first2 = A. | last3 = Ballinger | first3 = M. | last4 = Kowanetz | first4 = M. | last5 = Vansteenkiste | first5 = J. | last6 = Mazieres | first6 = J. | last7 = Park | first7 = K. | last8 = Smith | first8 = D. | last9 = Artal-Cortes | first9 = A. | title = Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. | journal = Lancet | volume = | issue = | pages = | month = Mar | year = 2016 | doi = 10.1016/S0140-6736(16)00587-0 | PMID = 26970723 }}</ref> | **Atezolizumab (''Tecentriq'', Roche).<ref name=pmid26970723>{{Cite journal | last1 = Fehrenbacher | first1 = L. | last2 = Spira | first2 = A. | last3 = Ballinger | first3 = M. | last4 = Kowanetz | first4 = M. | last5 = Vansteenkiste | first5 = J. | last6 = Mazieres | first6 = J. | last7 = Park | first7 = K. | last8 = Smith | first8 = D. | last9 = Artal-Cortes | first9 = A. | title = Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. | journal = Lancet | volume = | issue = | pages = | month = Mar | year = 2016 | doi = 10.1016/S0140-6736(16)00587-0 | PMID = 26970723 }}</ref> | ||
**Durvalumab. | **Durvalumab (''Imfinzi'', AstraZeneca). | ||
**Avelumab | **Avelumab (''Bavencio'', Merck/Pfizer). | ||
===Anti-PD-L1 drugs - use=== | ===Anti-PD-L1 drugs - use=== | ||