Expression of programmed death ligand (PD-L1) in different tumors. Comparison of several current available antibody clones and antibody profiling

Kintsler, Svetlana; Cassataro, Maria Angela; Drosch, Michael; Holenya, Pavlo; Knuechel, Ruth; Braunschweig, Till

doi:10.1016/j.anndiagpath.2019.05.005

Cited by 41 publications

(37 citation statements)

References 32 publications

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“…Several PD-L1 assays are available in oncology, and they seem to be highly interchangeable in HNSCC (52), specially for assays evaluating tumor cells by the antibodies SP263, 22C3, and 28-8 (53). Concordance between staining scores that involve immune cells, and/or other antibodies (e.g., SP142) are more modest (53,54) and require more careful interpretation. In the pivotal phase 3 Checkmate-141 trial, OS and ORR were improved by nivolumab across the entire study population.…”

Section: Predictive Factors For Immunotherapy Benefitsmentioning

confidence: 99%

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021

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Preclinical data suggest that head and neck squamous cell carcinomas (HNSCC) may evade immune surveillance and induce immunosuppression. One mechanism of immune evasion involves the expression of programmed death ligand-1 (PD-L1) in tumor and immune cells, which is, to date, the only biomarker routinely used in clinical practice to select patients with advanced HNSCCs more likely to benefit from anti-PD-1 therapy. Nonetheless, PD-L1 expression alone incompletely captures the degree of sensitivity of HNSCCs to PD-1 inhibitors. Most patients exposed to anti-PD-1 antibodies do not respond to therapy, suggesting the existence of mechanisms of de novo resistance to immunotherapy. Furthermore, patients that initially respond to PD-1 inhibitors will eventually develop acquired resistance to immunotherapy through mechanisms that have not yet been completely elucidated. In this article, we will provide an overview of the immune landscape of HNSCCs. We will briefly describe the clinical activity of inhibitors of the PD-1/PD-L1 axis in this disease, as well as biomarkers of benefit from these agents that have been identified so far. We will review pre-clinical and clinical work in cancers in general, and in HNSCCs specifically, that have characterized the mechanisms of de novo and acquired resistance to immunotherapy. Lastly, we will provide insights into novel strategies under investigation to overcome resistance to immune checkpoint inhibitors.

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Section: Predictive Factors For Immunotherapy Benefitsmentioning

confidence: 99%

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

2021

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“…However, as the 20% threshold was applied to various parameters of the total tissue cellularity, it is possible that this result arose due to selection or confirmation bias (34). Moreover, the use of different antibodies and dilution factors could account for the observed patterns due to false-positives as selected dilutions were not justified (37). Taking into consideration that EBV relationship to PD-L1 in tumour cell is unlikely, it is apparent that selected patients might benefit from targeted anti-PD-1 therapies as the 20% threshold relating PD-L1 to tumour microenvironment appears to show a more predominant EBV link to PD-L1 expression.…”

Section: Discussionmentioning

confidence: 99%

EBV Positivity and Programmed Death-ligand 1 Expression in Diffuse Large B-cell Lymphoma: A Systematic Review

Barzyk

Sheriff

2020

Anticancer Res

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“…PD‐L1 expression on both the tumor cells (tumor proportion score, TPS) and CD8 + T‐cell infiltrate (tumor‐infiltrating immune cells, IC) or both (combined positive score, CPS) have been explored as potential predictors of response to ICI. In addition, several antibodies for PD‐L1 are have been developed for use in performing immunohistochemical stains, and the expression pattern of PD‐L1 can be variable based on the antibody used and the operator's interpretation 68 . In KEYNOTE‐016, membranous PD‐L1 expression occurred only in patients with dMMR cancer and was prominent on tumor‐infiltrating lymphocytes and on tumor‐infiltrating macrophages located at the invasive fronts of the tumor ( p = .04) 34 .…”

Section: Predictors Of Response To Immunotherapymentioning

confidence: 99%

Immunotherapy for the treatment of colorectal cancer

Lumish

Cercek

2021

Journal of Surgical Oncology

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Immune checkpoint inhibition (ICI) has transformed the management of metastatic colorectal cancer (mCRC) with mismatch‐repair deficiency (dMMR) and microsatellite instability (MSI‐H), though this constitutes on average less than 5% of mCRC, and ICI is ineffective in preserved MMR/microsatellite stable disease (pMMR/MSS). Here we review the efficacy of ICI in dMMR/MSI‐H mCRC, poor response to ICI in pMMR/MSS mCRC, role for ICI in locally advanced disease, biomarkers of response, novel immunotherapies, and future directions in targeting resistance mechanisms.

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Expression of programmed death ligand (PD-L1) in different tumors. Comparison of several current available antibody clones and antibody profiling

Cited by 41 publications

References 32 publications

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

Overcoming Resistance to Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinomas

EBV Positivity and Programmed Death-ligand 1 Expression in Diffuse Large B-cell Lymphoma: A Systematic Review

Immunotherapy for the treatment of colorectal cancer

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