PD-L1 Expression as a Predictive Biomarker For Immune Checkpoint Inhibitors: Between a Dream And a Nightmare

Zouein, Joseph; Kesrouani, Carole; Kourié, Hampig Raphaël

doi:10.2217/imt-2020-0336

Cited by 19 publications

(9 citation statements)

References 70 publications

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“…Zhang et al discovered an association between PD-L1 expression and shorter OS in GC patients [ 26 ]. PD-L1 is also a predictive immune checkpoint inhibitor therapy marker [ 27 ]. PD-L1 plays the role of a “brake” in immune function, and immune checkpoint inhibition is effective in reactivating T cells and eliminating cancer cells [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer

Bao

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. The aim of this study was to analyze the association between the expression of chromatin assembly factor 1 subunit A (CHAF1A) in gastric cancer (GC) and clinicopathological features, disease prognosis, and expression of programmed cell death-ligand 1 (PD-L1). Material and Methods. A total of 140 GC tissue specimens were collected between January 2013 and December 2017. CHAF1A expression in GC and paracancerous tissues was determined. Then, the associations between CHAF1A expression level in the collected tissues and clinicopathological features as well as PD-L1 expression level were investigated. Cox regression analyses were carried out to determine whether CHAF1A is an independent prognostic factor for GC. Finally, the association between CHAF1A expression levels and survival of the GC patients was investigated. Results. A significantly higher level of CHAF1A expression in GC tissues was found compared to that in paracancerous tissues ( p = 0.042 ). CHAF1A expression level in GC tissues was found to be strongly associated with family history ( p = 0.005 ), smoking history ( p = 0.016 ), T stage ( p = 0.001 ), tumor marker AFP ( p = 0.017 ), tumor marker CEA ( p = 0.027 ), and PD-L1 expression ( p = 0.029 ). CHAF1A expression was also found to be positively correlated to PD-L1 expression ( p = 0.012 ). Moreover, high CHAF1A expression levels were found to lead to poor prognosis ( p = 0.019 ). Univariate and multivariate analyses all showed that CHAF1A was an independent poorer prognostic factor for gastric cancer ( p = 0.021 , HR = 1.175, 95% CI: 1.090–2.890 for univariate analyses; p = 0.014 , HR = 2.191, 95% CI:1.170–4.105 for multivariate analyses). A high level of CHAF1A expression was thus found to be an independent risk factor for GC prognosis. Conclusion. High CHAF1A expression is associated with poor GC prognosis and positively correlated to PD-L1 expression. Thus, CHAF1A expression level may be used as a novel biomarker for GC diagnosis.

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Section: Discussionmentioning

confidence: 99%

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer

Bao

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…4.1 | Molecular basis and limitations of clinical application of PD-1/PD-L1 blocking drugs PD-L1 expression is an important biomarker associated with tumour progression and is one of the FDA-approved biomarkers for assessing the effectiveness of immune checkpoint inhibitors (Zouein et al, 2021). Although PD-L1 positive expression is a logical prerequisite for PD-L1 antibody therapy, it is not always coincident with PD-L1 positivity and objective response rates of cancer patients.…”

Section: Clinical Perspective Of Pd-l1 Distribution-based Cancer Immu...mentioning

confidence: 99%

Optimization of cancer immunotherapy on the basis of programmed death ligand‐1 distribution and function

Zou

Luo

Gao

et al. 2023

British J Pharmacology

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Programmed cell death protein‐1 (PD‐1)/programmed death ligand‐1 (PD‐L1) immune checkpoint blockade as a breakthrough in cancer immunotherapy has shown unprecedented positive outcomes in the clinic. However, the overall effectiveness of PD‐L1 antibody is less than expected. An increasing number of studies have demonstrated that PD‐L1 is widely distributed and expressed not only on the cell membrane but also on the inside of the cells as well as on the extracellular vesicles secreted by tumour cells. Both endogenous and exogenous PD‐L1 play significant roles in influencing the therapeutic effect of anti‐tumour immunity. Herein, we mainly focused on the distribution and function of PD‐L1 and further summarized the potential targeted therapeutic strategies. More importantly, in addition to taking the overall expression abundance of PD‐L1 as a predictive indicator for selecting corresponding PD‐1/PD‐L1 monoclonal antibodies (mAbs), we also proposed that personalized combination therapies based on the different distribution of PD‐L1 are worth attention to achieve more efficient and effective therapeutic outcomes in cancer patients.

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“…Implementing immunohistochemical (IHC) testing for programmed death-ligand 1 (PD-L1) is a great field of interest for pathologists [ 1 , 2 , 3 ]. Several antibody clones were used in the context of “assays” associated with specific protocols, detection systems, and platforms, later approved by the Food and Drug Administration (FDA) as “companion diagnostics” (CDx) or as “complementary diagnostics” related to those specific immunotherapy drugs [ 1 , 3 , 4 , 5 , 6 ]. The combined positive score (CPS) is routinely required for head and neck squamous cell carcinomas (HNSCC) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Digital Pathology Applications for PD-L1 Scoring in Head and Neck Squamous Cell Carcinoma: A Challenging Series

Canini,

Eccher,

d’Amati

et al. 2024

JCM

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The assessment of programmed death-ligand 1 (PD-L1) combined positive scoring (CPS) in head and neck squamous cell carcinoma (HNSCC) is challenged by pre-analytical and inter-observer variabilities. An educational program to compare the diagnostic performances between local pathologists and a board of pathologists on 11 challenging cases from different Italian pathology centers stained with PD-L1 immunohistochemistry on a digital pathology platform is reported. A laboratory-developed test (LDT) using both 22C3 (Dako) and SP263 (Ventana) clones on Dako or Ventana platforms was compared with the companion diagnostic (CDx) Dako 22C3 pharm Dx assay. A computational approach was performed to assess possible correlations between stain features and pathologists’ visual assessments. Technical discordances were noted in five cases (LDT vs. CDx, 45%), due to an abnormal nuclear/cytoplasmic diaminobenzidine (DAB) stain in LDT (n = 2, 18%) and due to variation in terms of intensity, dirty background, and DAB droplets (n = 3, 27%). Interpretative discordances were noted in six cases (LDT vs. CDx, 54%). CPS remained unchanged, increased, or decreased from LDT to CDx in three (27%) cases, two (18%) cases, and one (9%) case, respectively, around relevant cutoffs (1 and 20, k = 0.63). Differences noted in DAB intensity/distribution using computational pathology partly explained the LDT vs. CDx differences in two cases (18%). Digital pathology may help in PD-L1 scoring, serving as a second opinion consultation platform in challenging cases. Computational and artificial intelligence tools will improve clinical decision-making and patient outcomes.

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PD-L1 Expression as a Predictive Biomarker For Immune Checkpoint Inhibitors: Between a Dream And a Nightmare

Cited by 19 publications

References 70 publications

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer

Optimization of cancer immunotherapy on the basis of programmed death ligand‐1 distribution and function

Digital Pathology Applications for PD-L1 Scoring in Head and Neck Squamous Cell Carcinoma: A Challenging Series

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