Journal
CANCER IMMUNOLOGY RESEARCH
Volume 3, Issue 12, Pages 1308-1315Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-15-0116
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Funding
- DF/HCC Kidney Cancer [SPORE P50CA101942, U54CA163125, P01AI056299]
- Claudia Adams Barr Program for Innovative Cancer Research
- AACR Basic Cancer Research Fellowship [14-40-01-MAHO]
- Kidney Cancer Association
- Center for Immuno-Oncology, Dana-Farber Cancer Institute
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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. (C)2015 AACR.
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