Tests immunohistochimiques PD-L1 dans les cancers du poumon non à petites cellules : recommandations par le groupe PATTERN de pathologistes thoraciques

Lantuéjoul, Sylvie; Adam, Julien; Girard, Nicolas; Duruisseaux, M.; Lupo, Audrey; Cazes, Aurélie; Rouquette, Isabelle; Gibault, Laure; García, Stéphane; Antoine, Martine; Vignaud, Julie; Galateau-Sallé, Françoise; Sagan, Christine; Badoual, Cécile; Penault‐Llorca, Frédérique; Damotte, Diane

doi:10.1016/j.annpat.2018.01.007

Cited by 20 publications

(7 citation statements)

References 41 publications

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“…The difficulty in correctly evaluating PD-L1 expression by IHC induces post-analytical heterogeneity, leading to intraand inter-observer discrepancies. The concordance data from the present study were similar to those from the DREAM study (11,22). Regarding PD-L1 TPS assessment in three categories, the present study reported intra-observer discrepancies between 16 and 17.5%, suggesting a hypothesis that, in daily practice, 1-2 out of 10 patients were potentially misdiagnosed.…”

Section: Discussionsupporting

confidence: 87%

“…The Checkmate 057 (6), Keynote 001 (7) and POPLAR (8) clinical studies demonstrated that, in NSCLC, high expression of PD-L1 in tumor cells is associated with a better response to IT; however the Checkmate 017 (9) study reported that some patients responded positively to nivolumab, another IT drug, although their lung tumor did not express PD-L1. At present, only the use of pembrolizumab is based on PD-L1 expression (1, 10,11).…”

Section: The Daily Practice Reality Of Pd-l1 (Cd274) Evaluation In Nomentioning

confidence: 99%

“…Conversely, previous studies reported a good agreement between histological and cytological samples, which are widely used in clinical routines (10,15,16). Cytological sample analysis could therefore be recommended routinely, although its use has not yet been validated in clinical trials (11). Secondly, it should be noted that for each IT molecule, a specific test for the evaluation of PD-L1 expression is developed (1).…”

Section: The Daily Practice Reality Of Pd-l1 (Cd274) Evaluation In Nomentioning

confidence: 99%

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The daily practice reality of PD‑L1 (CD274) evaluation in non‑small cell lung cancer: A retrospective study

et al. 2020

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Treatment with pembrolizumab, an anti-programmed cell death-1 (PDCD-1) monoclonal antibody for the treatment of non-small cell lung cancers (NSCLCs) requires prior immunohistochemical (IHC) analysis of the expression of the programmed death-ligand 1 (PD-L1) (also known as CD274 molecule) which is a heterogeneous and complex marker. The present study aimed to investigate how pathological and technical factors (such as tumor location and sampling type, respectively) may affect the PD-L1 evaluation in patients with NSCLC in the daily practice of pathology laboratories. The current study was retrospective, and included 454 patients with NSCLC, for whom PD-L1 expression analysis by IHC was prospectively performed between November 2016 and January 2018. The association between PD-L1 expression and the clinicopathological characteristics of patients was statistically investigated using either the χ 2 and Fisher exact tests or the Mann-Whitney and Kruskal-Wallis tests, depending on whether PD-L1 expression was assessed in three large categories (<1, 1-49, ≥50%) or in more precise percentages. Furthermore, the same statistical methodology was used to analyze the heterogeneity of PD-L1 expression according to its sampling type (cytology, biopsy or surgical specimen) and its location (primary tumor, lymph node or distant metastasis). Intra-and inter-observer discrepancies were also studied using double-blind evaluation and concordance analyses based on the weighted κ coefficient. The results demonstrated a significant association between PD-L1 expression and sample location (P=0.005), histological type (P=0.026), total number of mutations (P=0.004) and KRAS proto-oncogene, GTPase mutations (P=0.024). In addition, sampling type did not influence PD-L1 expression. The inter-and intra-observer discrepancies were 15% and between 16 and 17.5%, respectively. The present study confirmed that evaluation of PD-L1 expression by IHC can be performed on all types of samples. In addition, the results from the current study highlighted the heterogeneity of PD-L1 expression among the different types of sample location. In complex cases, a second evaluation of PD-L1 expression by IHC would be performed due to intraand inter-observer discrepancies.

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Section: Discussionsupporting

confidence: 87%

Section: The Daily Practice Reality Of Pd-l1 (Cd274) Evaluation In Nomentioning

confidence: 99%

Section: The Daily Practice Reality Of Pd-l1 (Cd274) Evaluation In Nomentioning

confidence: 99%

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The daily practice reality of PD‑L1 (CD274) evaluation in non‑small cell lung cancer: A retrospective study

et al. 2020

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“…Although the expression of PD-L1 could be used as a biomarker of response in immunotherapy, the expression of this protein before the start of treatment seems to be variable and no clear evidence has been found to assign its expression as a universal predictive biomarker. Nevertheless, its evaluation has been recently implemented as a potential biomarker for specific types of malignancies 37 . Regardless of the potential use of PD-L1 as an immunotherapeutic biomarker in patients undergoing immunotherapy, the up-regulation of this protein before immunotherapy treatments has been associated with poor prognosis in several types of malignancies 38 .…”

Section: Discussionmentioning

confidence: 99%

Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells

Knox

Sahakian

Banik

et al. 2019

Sci Rep

129

144

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Histone deacetylases (HDACs) are involved in diverse cellular regulatory mechanisms including non-canonical functions outside the chromatin environment. Several publications have demonstrated that selective HDAC inhibitors (HDACi) can influence tumor immunogenicity and the functional activity of specific immune cells. In particular, the selective inhibition of HDAC6 has been reported to decrease tumor growth in several malignancies. However, there is still no clarity about the cellular components mediating this effect. In this study, we evaluated the HDAC6i Nexturastat A as a priming agent to facilitate the transition of the tumor microenvironment from “cold” to “hot”, and potentially augment immune check-point blockade therapies. This combination modality demonstrated to significantly reduce tumor growth in syngeneic melanoma tumor models. Additionally, we observed a complete neutralization of the up-regulation of PD-L1 and other immunosuppressive pathways induced by the treatment with anti-PD-1 blockade. This combination also showed profound changes in the tumor microenvironment such as enhanced infiltration of immune cells, increased central and effector T cell memory, and a significant reduction of pro-tumorigenic M2 macrophages. The evaluation of individual components of the tumor microenvironment suggested that the in vivo anti-tumor activity of HDAC6i is mediated by its effect on tumor cells and tumor-associated macrophages, and not directly over T cells. Overall, our results indicate that selective HDAC6i could be used as immunological priming agents to sensitize immunologically “cold” tumors and subsequently improve ongoing immune check-point blockade therapies.

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“…In lung cancer, several immunotherapies targeting PD1/PD-L1 are approved: durvalumab, atezolizumab, nivolumab and pembrolizumab. Positive PD-L1 expression is required for pembrolizumab (stage IV) and durvalumab (unresectable stage III in some countries/regions) in not only squamous cell carcinoma but also non-squamous cell carcinoma [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma

et al. 2020

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Bronchial dysplasia is the pre-neoplastic lesion recognized for invasive squamous cell carcinoma. The mechanisms leading to invasive squamous cell carcinoma for this lesion are not fully known. Programmed Death-Ligand 1 (PD-L1) expression by the bronchial dysplasia neoplastic epithelium might suggest a response to immunotherapy. The objective of this work is to further characterize PD-L1 and CD8 expression in bronchial dysplasia and bronchial metaplasia compared to normal bronchial epithelium. Immunohistochemical analysis of PD-L1 and CD8 staining were characterized in bronchial dysplasia of 24 patients and correlated with clinical data. We also compared PD-L1 expression in dysplasia samples to 30 normal epithelium and 20 samples with squamous bronchial metaplasia. PD-L1 was never expressed in normal epithelium and in metaplastic epithelium whereas 37.5% of patients with bronchial dysplasia were stained by PD-L1 (p < 0.001). PD-L1 expression was not related to the degree of dysplasia or a medical history of invasive squamous cell carcinoma, while CD8 expression and its localization were related to medical history of squamous cell carcinoma (p = 0.044). Our results show that PD-L1 is expressed in roughly one third of patients with bronchial dysplasia and is not expressed in normal and metaplastic epithelium. This suggests that PD-L1 is expressed in preneoplastic lesions of squamous cell carcinoma.

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Tests immunohistochimiques PD-L1 dans les cancers du poumon non à petites cellules : recommandations par le groupe PATTERN de pathologistes thoraciques

Cited by 20 publications

References 41 publications

The daily practice reality of PD‑L1 (CD274) evaluation in non‑small cell lung cancer: A retrospective study

The daily practice reality of PD‑L1 (CD274) evaluation in non‑small cell lung cancer: A retrospective study

Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells

Immune Escape Is an Early Event in Pre-Invasive Lesions of Lung Squamous Cell Carcinoma

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