PD-L1 testing, fit for routine evaluation? From a pathologist's point of view - PubMed (original) (raw)

Review

PD-L1 testing, fit for routine evaluation? From a patholo gist's point of view

Georg Hutarew. Memo. 2016.

Abstract

Tumours with high somatic mutation rates escape immune surveillance by upregulating receptors and ligands such as programmed death receptor-1 and its ligand (PD-1/PD-L1). Checkpoint inhibitors (ICI) provide encouraging therapeutic results in non-small cell lung cancers (NSCLC) and may soon be used in 2nd or 1st line therapy. Currently PD-L1 immunohistochemistry (IHC) expression assessed on tumour cells is used as a predictive biomarker, since better patient outcomes are often, but not always associated with increased tumour cell PD-L1 IHC expression. However pre-analytical variables, different anti-PD-L1 clones used on different staining platforms, different specimens types, as well as intra- and interobserver variability influence the results. We will only understand PD-L1 expression on tumour cells if we accept that PD-L1 is an inducible pathophysiological factor with variable levels of PD-L1 expression depending on the immunological status. Should we test PD-L1 during initial diagnostic work up before, or at the point when immune checkpoint therapy is considered? Taking all arguments into account the value of PD-L1 as a predictive biomarker is questionable. Other predictive biomarkers such as high mutation burden, mRNA expression, neo-antigens and the diversity of tumour antigen-specific T cells should be evaluated in the future. Here we review results presented in 30 journal articles and three reviews covering this topic in the last 3 years.

Keywords: Biomarker assay; Immune checkpoint inhibitors; Immunohistochemistry; PD-1; PD-L1.

PubMed Disclaimer

Conflict of interest statement

Conflict of interestG. Hutarew declares that he has no competing interests.

Figures

Fig. 1

Fig. 1

Pulmonary adenocarcinoma. a HE and b positive TTF1 staining, both images ×100 magnification

Fig. 2

Fig. 2

Images of the TTF1 + pulmonary adenocarcinoma seen in Fig. 1 stained positive with different PD-L1 antibody clones, Cross-testing, (a,b) Abcam 28-8 and Cell Signaling E1L3N and, both stained on Ventana Ultra with OptiView, (c,d) DAKO Pharm DX 22C3 and Ventana SP263, both prepackaged kits. Scoring does not evaluate intensity therefore enhancement systems such as OptiView can be used without altering the results. All images ×100 magnification

Similar articles

Cited by

References

    1. Kerr KM, Nicolson MC. Non-small cell lung cancer, PD-L1, and the pathologist. Arch Pathol Lab Med. 2016;140:249–254. doi: 10.5858/arpa.2015-0303-SA. - DOI - PubMed
    1. Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339:1546–1558. doi: 10.1126/science.1235122. - DOI - PMC - PubMed
    1. Lawrence MS, Stojanov P, Polak P, et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. 2013;499:214–218. doi: 10.1038/nature12213. - DOI - PMC - PubMed
    1. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–567. doi: 10.1038/nature14011. - DOI - PMC - PubMed
    1. Hamanishi J, Mandai M, Matsumura N, et al. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. Int. J. Clin. Oncol. 2016;21:462–473. doi: 10.1007/s10147-016-0959-z. - DOI - PMC - PubMed

Publication types

LinkOut - more resources