Lynette M. Sholl, Dara L. Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain C. Borczuk, Philip T. Cagle, Vera Capelozzi, Sanja Dacic, Lida Hariri, Keith M. Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Eric Thunnissen, Ming Sound Tsao, and Yasushi Yatabe (2016) Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

Lynette M. Sholl, MD; Dara L. Aisner, MD; Timothy Craig Allen, MD, JD; Mary Beth Beasley, MD; Alain C. Borczuk, MD; Philip T.Cagle, MD; Vera Capelozzi, MD, PhD; Sanja Dacic, MD, PhD; Lida Hariri, MD, PhD; Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE;Sylvie Lantuejoul, MD, PhD; Mari Mino-Kenudson, MD; Kirtee Raparia, MD; Natasha Rekhtman, MD, PhD; Sinchita Roy-Chowdhuri,MD, PhD; Eric Thunnissen, MD, PhD; Ming Sound Tsao, MD; Yasushi Yatabe, MD, PhD; for the members of the Pulmonary Pathology Society

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Dr Sholl); the Department of Pathology, University of Colorado Cancer Center, Denver (Dr Aisner); the Department of Pathology, The University of Texas Medical Branch, Galveston (Dr Allen); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Beasley); the Department of Pathology, Weill Cornell Medical College, New York, New York (Drs Borczuk and Cagle); the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil (Dr Capelozzi); the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Dacic); the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston (Drs Hariri and Kenudson); the Department of Pathology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, United Kingdom (Dr Kerr); the Department of Biopathology, Centre Léon Bérard, Lyon, and J Fourier University– INSERM U 823-Institut A Bonniot, Grenoble, France (Dr Lantuejoul); the Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois (Dr Raparia); the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (Dr Rekhtman); the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Roy-Chowdhuri); the Department of Pathology, VU Medical Center, Amsterdam, the Netherlands (Dr Thunnissen); the Department of Pathology, University Health Network, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada (Dr Tsao); and the Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan (Dr Yatabe).

 Dr Sholl received consultancy honoraria from Genentech. Dr Rekhtman received consultancy honoraria from Bristol-Myers Squibb. Dr Beasley is a member of the Genentech Scientific Advisory Board. Dr Kerr receives lecture fees and/or advisory fees from Astra-Zeneca, Roche-Genentech, Bristol-Myers Squibb, Merck, and Pfizer. Dr Tsao received consultancy honoraria from Pfizer, Merck Canada, AstraZeneca, and Roche-Genentech. Dr Thunnissen is on the Global Advisory Board for Merck and only receives cost for travel. The other authors have no relevant financial interest in the products or companies described in this article.

Reprints: Timothy Craig Allen, MD, JD, Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (email: tcallen@utmb.edu).

The binding of programmed death ligands 1 and 2 (PD-L1 and PD-L2) to PD-1 blocks T-cell–mediated immune response to tumor. Antibodies that target programmed death 1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non–small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non–small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay–one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.