2. Academic Validation
  3. PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells

PD-L1 Antibodies to Its Cytoplasmic Domain Most Clearly Delineate Cell Membranes in Immunohistochemical Staining of Tumor Cells

  • Cancer Immunol Res. 2015 Dec;3(12):1308-15. doi: 10.1158/2326-6066.CIR-15-0116.
Kathleen M Mahoney 1,  Heather Sun 2,  Xiaoyun Liao 3,  Ping Hua 4,  Marcella Callea 2,  Edward A Greenfield 4,  F Stephen Hodi 3,  Arlene H Sharpe 5,  Sabina Signoretti 2,  Scott J Rodig 6,  Gordon J Freeman 7
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
  • 2 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. Center for Immuno-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
  • 4 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
  • 5 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
  • 6 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Center for Immuno-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
  • 7 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. gordon_freeman@dfci.harvard.edu.
PMID: 26546452 DOI: 10.1158/2326-6066.CIR-15-0116
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.

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