Difference between revisions of "Programmed death-ligand 1"
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'''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is a protein with an important role in | '''Programmed death-ligand 1''', commonly abbreviated '''PD-L1''', is a protein with an important role in immune system regulation and [[cancer]]. | ||
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== | ||
*[[IHC]] | *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">{{Cita publicación | apellido = Scheel | nombre = AH. | coautores = M. Dietel, LC. Heukamp, K. Jöhrens, T. Kirchner, S. Reu, J. Rüschoff, HU. Schildhaus, P. Schirmacher, M. Tiemann, A. Warth | título = Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. | publicación = Mod Pathol | volume = 29 | número = 10 | páginas = 1165-72 | mes = Oct | año = 2016 | doi = 10.1038/modpathol.2016.117 | pmid = 27389313 }}</ref> | **Carcinoma cell is considered "PD-L1 positive" if the cell membrane is partially or completely stained. <ref name="pmid27389313">{{Cita publicación | apellido = Scheel | nombre = AH. | coautores = M. Dietel, LC. Heukamp, K. Jöhrens, T. Kirchner, S. Reu, J. Rüschoff, HU. Schildhaus, P. Schirmacher, M. Tiemann, A. Warth | título = Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. | publicación = Mod Pathol | volume = 29 | número = 10 | páginas = 1165-72 | mes = Oct | año = 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. | |||
*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. | ||
**Nivolumab - 28-8 (Dako) | **Nivolumab - 28-8 (Dako) | ||
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*[[Renal cell carcinoma]]. | *[[Renal cell carcinoma]]. | ||
*[[Urothelial carcinoma]]. | *[[Urothelial carcinoma]]. | ||
*[[Merkel cell carcinoma]] | |||
*[[Acute myeloid leukemia]] | |||
==See also== | ==See also== | ||
Revision as of 21:25, 28 November 2017
Programmed death-ligand 1, commonly abbreviated PD-L1, is a protein with an important role in immune system regulation and cancer.
Normally, PD-L1 on cells binds with programmed cell death 1 on the T lymphocytes.[1]
PD-L1 is also known as CD274.[2]
General
- In theory, positive PD-L1 immunostaining predicts response to anti-PD-L1 drugs.[3]
- Carcinoma cell is considered "PD-L1 positive" if the cell membrane is partially or completely stained. [4]
- 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.
- Nivolumab - 28-8 (Dako)
- Pembrolizumab - 22C3 (Dako)
- Aterolizumab - SP142 (Ventana)
- Durvalumab - SP263 (Ventana)
- Avelumab - 73-10 (Dako)
Background
Cytotoxic T cell function is regulated by receptor pairs found on the tumour and lymphocyte:[1]
| Function | Tumour cell | T cell |
|---|---|---|
| Antigen presentation | MHC | TCR |
| Signal inhibition | PD-1 | PD-L1 (CD274), PD-L2 (CD273) |
Prognosis
- Good prognosis - in high-grade ovarian serous carcinoma, associated with tumour-infiltrating lymphocytes.[5]
Drugs - Immune checkpoint inhibitors
- PD-1 inhibitors:
- Nivolumab
- Pembrolizumab
- PD-L1 inhibitors:
- Atezolizumab.[3]
- Durvalumab.
- Avelumab
Anti-PD-L1 drugs - use
PD-L1 antibodies are being used to treat:[6]
- Malignant melanoma.
- Non-small cell lung cancer.
- Associated with response predicted by tumour-infiltrating lymphocytes and PD-L1 IHC positivity of the tumour cells.[3]
- Renal cell carcinoma.
- Urothelial carcinoma.
- Merkel cell carcinoma
- Acute myeloid leukemia
See also
References
- ↑ 1.0 1.1 Ribas, A. (Jun 2012). "Tumor immunotherapy directed at PD-1.". N Engl J Med 366 (26): 2517-9. doi:10.1056/NEJMe1205943. PMID 22658126.
- ↑ Online 'Mendelian Inheritance in Man' (OMIM) 605402
- ↑ 3.0 3.1 3.2 Fehrenbacher, L.; Spira, A.; Ballinger, M.; Kowanetz, M.; Vansteenkiste, J.; Mazieres, J.; Park, K.; Smith, D. et al. (Mar 2016). "Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial.". Lancet. doi:10.1016/S0140-6736(16)00587-0. PMID 26970723.
- ↑ Template:Cita publicación
- ↑ Webb, JR.; Milne, K.; Kroeger, DR.; Nelson, BH. (May 2016). "PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer.". Gynecol Oncol 141 (2): 293-302. doi:10.1016/j.ygyno.2016.03.008. PMID 26972336.
- ↑ Gandini, S.; Massi, D.; Mandalà, M. (Apr 2016). "PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: A systematic review and meta-analysis.". Crit Rev Oncol Hematol 100: 88-98. doi:10.1016/j.critrevonc.2016.02.001. PMID 26895815.