Programmed death-ligand 1

From Libre Pathology
(Redirected from PD-L1)
Jump to navigation Jump to search
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.

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.[1]

PD-L1 is also known as CD274.[2]


PD-L1 positive lung adenocarcinoma in a lymph node. 22C3 PD-L1 immunostain. (WC)
  • 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)


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)


Drugs - Immune checkpoint inhibitors

  • PD-1 inhibitors:
    • Nivolumab (Opdivo, Bristol-Myers Squibb).
    • Pembrolizumab (Keytruda, Merck).
  • PD-L1 inhibitors:
    • Atezolizumab (Tecentriq, Roche).[3]
    • Durvalumab (Imfinzi, AstraZeneca).
    • Avelumab (Bavencio, Merck/Pfizer).

Anti-PD-L1 drugs - use

PD-L1 antibodies are being used to treat:[6]

See also


  1. 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.
  2. Online 'Mendelian Inheritance in Man' (OMIM) 605402
  3. 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.
  4. Scheel, AH.; Dietel, M.; Heukamp, LC.; Jöhrens, K.; Kirchner, T.; Reu, S.; Rüschoff, J.; Schildhaus, HU. et al. (Oct 2016). "Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas.". Mod Pathol 29 (10): 1165-72. doi:10.1038/modpathol.2016.117. PMID 27389313.
  5. 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.
  6. 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.