A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies

Batenchuk, Cory; Albitar, Mäher; Zerba, Kim E.; Sudarsanam, Sucha; Chizhevsky, Vladislav; Jin, Chelsea; Burns, Virginia

doi:10.1136/jclinpath-2018-205362

Cited by 35 publications

(31 citation statements)

References 27 publications

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“…Of note, the AT-TRACTION-2 study showed that nivolumab had significant benefit in all patients, regardless of PD-L1 expression [46]. The PD-L1 IHC 28-8 pharmDx assay gained FDA approval as a complementary diagnostic test for nivolumab as second line treatment for advanced non-small cell lung cancer (NSCLC) [67].…”

Section: Ihc Of Pd-l1mentioning

confidence: 99%

Tumor immune response and immunotherapy in gastric cancer

Kwak

Seo

Lee

et al. 2020

J Pathol Transl Med

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Recent studies have reported the promising results of immunotherapy in many solid tumors [1]. Unlike traditional cancer therapy, which targets the tumor directly, immunotherapy offers a different approach and is an alternative treatment option for patients with cancer. Because immunotherapy generally engages immune reactions to recognize and eliminate tumor cells, demand for understanding the tumor immune response has increased. Resulting from increased study, novel biomarkers associated with the tumor immune reaction have emerged. These biomarkers may allow innovative approaches in patient selection for immunotherapy and lead to advanced treatment response, expanding the potential impact of immunotherapy. After the advent of U.S. Food and Drug Administration (FDA)-approved anti-programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy agents, the importance of immunotherapy in gastric cancer (GC) has continuously increased. In this review article, we recapitulate the general concept of immuno-oncology and discuss its clinical application while focusing on historical and current clinical trials.

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Section: Ihc Of Pd-l1mentioning

confidence: 99%

Tumor immune response and immunotherapy in gastric cancer

Kwak

Seo

Lee

et al. 2020

J Pathol Transl Med

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“…There are currently four FDA approved PD-L1 IHC assays as companion and/or complementary diagnostic tests, with different antibodies, cut points, scoring systems and cell specific expression associated with each test resulting in confusion in pathology labs for patients and their physicians. Since many studies have showed variable results with current assays [ 8 – 15 ], we have begun efforts to generate more quantitative and reproducible results. While DSP is not ready for the clinic, the technology behind the platform shows the kind of robustness and reproducibility that is typical for laboratory medicine pathology tests (generally better than IHC).…”

Section: Discussionmentioning

confidence: 99%

“…Each assay is read subjectively by a pathologist with a range of cutoffs defining expression positivity and cell specific expression either in tumor cell (TC) and/or immune cells (IC) [ 5 – 7 ]. Harmonization studies have been done to compare the assays within specific tumor types [ 8 – 15 ]. Despite strong agreement in TC PD-L1 IHC scoring among experienced pathologists, there is a poor concordance in IC PD-L1 IHC scoring or low PD-L1 scores [ 8 , 12 , 14 – 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Harmonization studies have been done to compare the assays within specific tumor types [ 8 – 15 ]. Despite strong agreement in TC PD-L1 IHC scoring among experienced pathologists, there is a poor concordance in IC PD-L1 IHC scoring or low PD-L1 scores [ 8 , 12 , 14 – 17 ]. This diversity of assays and scoring systems has led to confusion amongst both oncologists and pathologist.…”

Section: Introductionmentioning

confidence: 99%

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Digital quantitative assessment of PD-L1 using digital spatial profiling

Gupta

Zugazagoitia

Martinez-Morilla

et al. 2020

Laboratory Investigation

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The assessment of programmed death 1 ligand 1 (PD-L1) expression by Immunohistochemistry (IHC) is the US Food and Drug Administration (FDA)-approved predictive marker to select responders to checkpoint blockade anti-PD-1/PD-L1 axis immunotherapies. Different PD-L1 immunohistochemistry (IHC) assays use different antibodies and different scoring methods in tumor cells and immune cells. Multiple studies have compared the performance of these assays with variable results. Here, we investigate an alternative method for assessment of PD-L1 using a new technology known as digital spatial profiling. We use a previously described standardization tissue microarray (TMA) to assess the accuracy of the method and compare digital spatial profiler (DSP) to each FDA approved PD-L1 assay and one LDT assay and 3 quantitative fluorescence assays. The standardized cell line Index tissue microarray contains 10 isogenic cells lines in triplicates expressing various range of PD-L1. The dynamic range of PD-L1 digital counts was measured in the ten cell lines on the Index TMA using GeoMx DSP assay and readout on the nCounter platform. The digital method shows very high correlation with immunohistochemistry scored with quantitative software and with quantitative fluorescence. High correlation of PD-L1 digital DSP counts were seen between rows on the same Index TMA. Finally, experiments from two Index TMAs showed reproducibility of DSP counts were independent of variable slide storage time over a three-week period after antibody labeling but before collection of cleaved tags. In summary, DSP appears to have quantitative potential comparable to quantitative immunohistochemistry. It is possible that this technology could be used as a PD-L1 protein measurement system for companion diagnostic testing for immune therapy.

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“…IHC staining was performed using anti-PD-L1 antibody (1 : 500) (clone 28-8, Abcam, Cambridge, UK) [ 21 – 24 ], anti-CD4 antibody (1 : 500) (clone EPR6855, Abcam, Cambridge, UK), anti-CD8 antibody (1 : 200) (rabbit polyclonal anti-CD8, Abcam, Cambridge, UK), anti-CD163 antibody (1 : 500) (clone EPR19518, Abcam, Cambridge, UK), and anti-FoxP3 antibody (1 : 100) (clone 236A/E7, Abcam, Cambridge, UK) as the primary antibodies.…”

Section: Methodsmentioning

confidence: 99%

Tumor-Infiltrating Immune Cells and PD-L1 as Prognostic Biomarkers in Primary Esophageal Small Cell Carcinoma

Ni³

et al. 2020

Journal of Immunology Research

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Primary esophageal small cell carcinoma (PESCC) is a weakly prevalent but lethal malignancy with early metastasis and a poor prognosis. Currently, neither effective prognostic indicators nor curative therapies are available for PESCC. Immunotherapy has now evolved into one of the most promising therapies for cancer patients. Tumor-infiltrating immune cells which are integral to the tumor immune microenvironment (TIME) are recognized as highly important for prognosis prediction, while the responsiveness to immune checkpoint blockade may be subject to the features of TIME. In this study, we aim to identify the TIME and provide indication for the applicability of immune checkpoint therapy in PESCC. We found that PD-L1 expression was detected in 33.33% (27/81) of all the patients, mostly exhibiting a stroma-only pattern and that it was positively associated with tumor-infiltrating immune cells (CD4+, CD8+, and CD163+). In 74.07% of PD-L1-positive specimens, PD-L1+CD163+ cells were colocalized more with CD4+ than CD8+ T cells. 83.95% (68/81) of all the specimens were infiltrated with more CD4+ than CD8+ T cells. Further analysis showed FoxP3+ Tregs constituted 13-27% of the total CD4+ T cell population. The Kaplan-–Meier analysis indicated several factors that contribute to poor survival, including negative PD-L1 expression, rich CD4 expression, rich FoxP3 expression, a low CD8/CD4 ratio, and a high FoxP3/CD8 ratio. A nomogram model was constructed and showed good performance for survival prediction. These results highlight that a suppressive TIME contributes to poor survival of patients with PESCC. TIME analyses might be a promising approach to evaluate the possibility and effect of immune checkpoint-based immunotherapeutics in PESCC patients.

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A real-world, comparative study of FDA-approved diagnostic assays PD-L1 IHC 28-8 and 22C3 in lung cancer and other malignancies

Cited by 35 publications

References 27 publications

Tumor immune response and immunotherapy in gastric cancer

Tumor immune response and immunotherapy in gastric cancer

Digital quantitative assessment of PD-L1 using digital spatial profiling

Tumor-Infiltrating Immune Cells and PD-L1 as Prognostic Biomarkers in Primary Esophageal Small Cell Carcinoma

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