@article {702916,
	title = {PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells.},
	journal = {Cancer Immunol Res},
	volume = {3},
	number = {12},
	year = {2015},
	month = {2015 Dec},
	pages = {1308-15},
	abstract = {Blocking the programmed death-1 (PD-1) pathway has clinical benefit in metastatic cancer and has led to the approval of the mAbs pembrolizumab and nivolumab to treat melanoma and nivolumab for non-small cell lung cancer. Expression of PD-L1 on the cell surface of either tumor cells or infiltrating immune cells is associated with a higher likelihood of response to PD-1 blockade in multiple studies. Most mAbs to PD-L1 in use are directed to its extracellular domain and immunohistochemically stain tumor tissue with a mixture of cytoplasmic and membrane staining. Cytoplasmic staining obscures the interpretation of a positive reaction on the tumor cell membrane, and thus affects the accuracy of PD-L1 scoring systems. We developed a mAb to the cytoplasmic domain of PD-L1, 405.9A11 (9A11), which is both more selective for membranous PD-L1 and more sensitive in IHC and Western blotting, compared with previous mAbs specific for the PD-L1 extracellular domain. Here, we compare immunohistochemical staining patterns of PD-L1 expression in five types of tumors, using five PD-L1 mAbs: 9A11, 7G11, and three commercially available mAbs. We demonstrate that 9A11, as well as two other cytoplasmic domain-specific mAbs, E1L3N and SP142, can clearly delineate the membrane of PD-L1-positive cells in formalin-fixed paraffin-embedded tissue and facilitate interpretation of staining results.},
	issn = {2326-6074},
	doi = {10.1158/2326-6066.CIR-15-0116},
	author = {Mahoney, Kathleen M and Sun, Heather and Liao, Xiaoyun and Hua, Ping and Callea, Marcella and Greenfield, Edward A and Hodi, F Stephen and Sharpe, Arlene H and Signoretti, Sabina and Rodig, Scott J and Freeman, Gordon J}
}
