Der prädiktive Wert der PD-L1-Diagnostik

Hu, Schildhaus

doi:10.1007/s00292-018-0507-x

Cited by 82 publications

(45 citation statements)

References 28 publications

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“…PD-L1 scoring (TPS, CPS, and IC) was performed as reviewed by Schildhaus et al using the following criteria [12]: tumor proportion score, TPS: percentage of viable tumor cells showing partial or complete membrane PD-L1 staining at any intensity (only membranous staining), combined positive/positivity score, CPS: number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by the total number of viable tumor cells, multiplied by 100, immune cell (IC) score: percentage of tumor area covered by PD-L1 + immune cells (4-tiered score: 0: <1%, 1: 1-5%, 2: 5-10%, 3: >10%. Quality and reliability of PD-L1 scoring (TPS, CPS, and IC) has been evaluated through regular interlaboratory ring trials coordinated by the ''Qualitätssicherungsinitiative Pathologie" (QuIP) GmbH (https://quip.eu) [12].…”

Section: Pd-l1 Scoringmentioning

confidence: 99%

“…Immune checkpoint inhibition constitutes a well-established approach in the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), malignant melanoma (MM), urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC), and Hodgkin lymphoma (HL) in a relapsed or refractory setting [10,11]. Since tumor cells evade the cytotoxic T-cell-response by surface expression of modulatory checkpoint proteins, immunohistochemistry (IHC) for PD-L1 expression on tumor and/or immune cells has been proven to be a prognostic biomarker for the response to checkpoint inhibition [12]. However, different scoring methods and cutoffs for the various IHC assays and tumor entities have, so far, been established.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

Witte

Gebauer

Lappöhn

et al. 2020

Cancers

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Background: Malignant neoplasms of the salivary glands are rare, and therapeutic options are limited. Results from recently published studies indicate a possible use for checkpoint inhibition in a subset of patients, but there are no established criteria for programme cell death ligand 1 (PD-L1) scoring in salivary gland carcinomas (SGCs). Methods: In this retrospective study, we present a cohort of 94 SGC patients with full clinical follow-up. We included 41 adenoid cystic carcinomas (AdCC), 21 mucoepidermoid carcinomas (MEC), 16 acinic cell carcinomas (ACC), 12 adenocarcinomas, not otherwise specified (AC, NOS), 2 epithelial-myoepithelial carcinomas (EMC), one salivary duct carcinoma (SDC), and one carcinoma ex pleomorphic adenoma (CA ex PA). Subsequent histopathological analysis was performed with special emphasis on the composition of the immune cell infiltrate (B-/T-lymphocytes). We assessed PD-L1 (SP263) on full slides by established scoring criteria: tumor proportion score (TPS), combined positivity score (CPS) and immune cell (IC) score. Results: We identified significantly elevated CD3+, TP, CP, and IC scores in AC, NOS compared to AdCC, MEC, and ACC. CPS correlated with node-positive disease. Moreover, AC, NOS displayed IC scores of 2 or 3 in the majority (67%) of cases (p = 0.0031), and was associated with poor prognosis regarding progression-free (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). CPS correlated with strong nuclear or null p53 staining in AC, NOS but not in other SGCs. Long-lasting partial remission could be achieved in one AC, NOS patient who received Pembrolizumab as third-line therapy. Conclusions: The current study is the first to investigate the use of established scoring criteria for PD-L1 expression in malignant salivary gland tumors. Our findings identify unique characteristics for AC, NOS among the family of SGCs, as it is associated with poor prognosis and might represent a valuable target for immune checkpoint inhibition.

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Section: Pd-l1 Scoringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

Witte

Gebauer

Lappöhn

et al. 2020

Cancers

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“…PD-L1 was originally characterized as a ubiquitous antiapoptotic receptor on cancer cells [3] and it has been proposed as potential target in cancer immunotherapy in human clinic [24,25]. However, we found that cancer cells (CD10+ and CD30+ cells) in AITL lacked the expression of PD-L1 ( Supplementary Fig.…”

Section: Discussionmentioning

confidence: 89%

“…Precise characterization of PD-L1-positive cells may contribute to our knowledge of which patients derive benefit from the PD-L1 blockade therapy [24,25]. This study was aimed at the immunophenotyping of the PD-1/PD-L1 axis in in Hodgkin lymphoma and in AITL.…”

Section: Introdutionmentioning

confidence: 99%

Immunophenotyping of the PD-L1-positive cells in angioimmunoblastic T cell lymphoma and Hodgkin disease

Tiemann

Samoilova

Atiakshin

et al. 2020

Preprint

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Objective Programmed Death-1(PD-1) and its ligand PD-L1 are now used as predictive biomarkers to guide clinical decisions. Precise characterization of PD-L1-positive cells may contribute to our knowledge of which patients derive benefit from the PD-L1 blockade therapy. Results To address this issue, we performed immunophenotyping of PD-L1-positive cells in Hodgkin lymphoma and in angioimmunoblastic T-cell lymphoma (AITL) employing multiple immunofluorescent immunolabeling. We found that PD-L1-positive cells and PD-1-positive cells both in Hodgkin lymphoma and in AITL belong to two completely different cell lineages. In both lymphomas, PD-1 was found exclusively in T-lymphocytes, whereas PD-L1 was revealed in the tumor microenvironment cells including macrophages. PD-L1 was also detected in CD30-positive cells in Hodgkin lymphoma but not in AITL. The marker of B-cell lineage, CD20, was not detectable in PD-L1-positive cells both in AITL and in Hodgkin. Our study highlights the importance of comprehensive assessment of PD-1/PD-L1 regulatory pathways for employing PD-L1 as a predictive biomarker in clinical practice. PD-L1-antibody therapy is proven in Hodgkin lymphoma. Comparative immunophenotyping of the PD-1/PD-L1 axis provides a support for attempts to prove this principle also for AITL.

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“…Correspondingly, patients with overexpressed PD-L1 in the tumor microenvironment, have improved clinical outcomes with anti-PD-1/PD-L1-directed therapy [33]. It was earlier reported that PD-L1 is stronger presented in the tumor microenvironment then PD-1 [34] and PD-L1 has been proposed as a potential target in cancer immunotherapy in human clinic [33,35]. Therefore, PD-L1 expression in the tumor tissue can be regarded as a more valuable biomarker than PD-1 to guide clinical decisions.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint proteins CTLA-4, PD-1 and PD-L1 in melanoma as predictive biomarkers to guide clinical decisions

Tiemann

Samoilova

Atiakshin

et al. 2020

Preprint

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Background CTLA-4, PD-1 and PD-L1 are potential targets in cancer immunotherapy. However, to predict patients who are likely to respond to treatment with PD-1/PD-L1/CTLA-4 blockers still remains a challenge. Unfortunately, it is often ignored that CTLA-4 exists also in cells other than lymphocytes. This study aimed to assess the expression and diagnostic significance of predictive biomarkers for melanoma. Methods To address this issue, we performed an immunophenotyping of CTLA4/PD1/PD-L1-positive cells in melanoma employing multiple immunofluorescent immunolabeling. For immunolabeling, we used primary antibodies to PD-1 and PD-L1, a panel of anti–CTLA-4 antibodies of different clones and a panel of CD antibodies against diverse cell types (CD1a, CD3, CD8 and CD68). Results In contrast to the currently accepted view, immunolabeling with anti-CTLA-4 antibodies of different clones permitted to reveal CTLA-4 in cells other than lymphocytes. CTLA-4 and PD-L1 are both expressed in the tumor microenvironment cells including antigen-presenting cells ÷ macrophages and dendritic cells. PD-1 is expressed solely in T-lymphocytes. CTLA-4 and PD-L1 in melanoma are not expressed in malignant cells. Conclusion Accordingly, PD-L1 expression by tumor cells cannot serve as a biomarker of clinical response to checkpoint blockade in melanoma immunotherapy, but PD-L1 and CTLA-4 expressed in the tumor microenvironment cells are valuable biomarkers to guide clinical decisions. The expression of CTLA-4 also in cells other than T-lymphocytes suggests the involvement of this molecule in alternative CTLA-4 signaling pathways together with the well-known classical scheme for the regulation of T-lymphocyte activity.

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Der prädiktive Wert der PD-L1-Diagnostik

Cited by 82 publications

References 28 publications

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

Prognostic Impact of PD-L1 Expression in Malignant Salivary Gland Tumors as Assessed by Established Scoring Criteria: Tumor Proportion Score (TPS), Combined Positivity Score (CPS), and Immune Cell (IC) Infiltrate

Immunophenotyping of the PD-L1-positive cells in angioimmunoblastic T cell lymphoma and Hodgkin disease

Immune checkpoint proteins CTLA-4, PD-1 and PD-L1 in melanoma as predictive biomarkers to guide clinical decisions

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