Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

Igawa, Satoshi; Sato, Yuichi; Ryuge, Shinichiro; Ichinoe, Masaaki; Katono, Ken; Hiyoshi, Yasuhiro; Otani, Sakiko; Nagashio, Ryo; Nakashima, Hiroyasu; Katagiri, Masayuki; Sasaki, Jiichiro; Murakumo, Yoshiki; Satoh, Yukitoshi; Masuda, Noriyuki

doi:10.1159/000458412

Cited by 37 publications

(26 citation statements)

References 40 publications

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“…An association between PD‐L1 and molecular mutations in NSCLC has been investigated with conflicting results. Some studies have documented an association between PD‐L1 expression and molecular alterations, including EGFR mutations, KRAS mutations, and ALK translocations, whereas other studies have failed to find such correlations . Our study did demonstrate a significant correlation of PD‐L1 expression (PD‐L1 positivity, high PD‐L1 expression, and expression levels) with KRAS mutations but not with any other mutations.…”

Section: Discussioncontrasting

confidence: 61%

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Programmed cell death ligand 1 expression in cytologic and surgical non–small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations

Mei

Shilo

Wei

et al. 2019

Cancer Cytopathology

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Background Programmed cell death ligand 1 (PD‐L1) expression by the 22C3 pharmDx companion assay has been validated in surgical specimens to support pembrolizumab treatment decisions for patients with non–small cell lung carcinoma (NSCLC). The aims of this study were 1) to assess the adequacy of cytologic specimens for PD‐L1 evaluation and 2) to explore correlations of PD‐L1 expression with clinicopathologic and molecular features. Methods The study cohort included 100 cytology specimens (fluid [n = 28] and fine‐needle aspiration [n = 72]) and 165 surgical specimens (biopsy [n = 138] and resection [n = 27]). The PD‐L1 immunohistochemistry 22C3 assay and staining assessment were performed according to the manufacturer's instructions. PD‐L1 expression was correlated with patients' demographics, pathologic characteristics, and molecular alterations. Results One hundred forty‐two specimens (53.6%) were positive for PD‐L1 expression (≥1%). No statistically significant difference in PD‐L1 expression was identified between cytologic (56.0%) and surgical specimens (52.1%). Seventy‐four of 190 tested cases (38.9%) had genetic alterations. PD‐L1 positivity was significantly more prevalent in cases with genetic alterations than in cases without genetic alterations. Furthermore, both PD‐L1 positivity and high PD‐L1 expression (≥50%) had statistically significant associations with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. PD‐L1 expression had no significant association with histologic phenotypes or other clinicopathologic features. Conclusions The data indicate that cytologic specimens are comparable to surgical specimens for PD‐L1 evaluation. The association of PD‐L1 expression with KRAS mutations may have clinical relevance in selecting patients with NSCLC for immunotherapy.

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Section: Discussioncontrasting

confidence: 61%

“…PD‐L1 expression has been observed to correlate with some clinicopathologic features, including smoking, an advanced tumor stage, and squamous cell carcinoma histology . However, other studies have failed to demonstrate such associations .…”

Section: Discussionmentioning

confidence: 99%

Programmed cell death ligand 1 expression in cytologic and surgical non–small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations

Mei

Shilo

Wei

et al. 2019

Cancer Cytopathology

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“…Conversely, in a retrospective Japanese study, multivariate logistic regression identified squamous histology to be independently associated with a higher objective response rate with nivolumab (67 vs 11%; p = 0.004) [63]. As squamous histology has been found to be independently associated with high expression of PD-L1 [64], it is likely that PD-L1 expression rather than tumor histology may underlie any difference seen between squamous and nonsquamous populations, and therefore may be biasing post hoc analyses. Due to the influence of PD-L1 expression, not to mention the association between smoking status and histology type, and the insufficient evidence for a survival benefit in one population over another, we do not recommend using histology as a factor to select patients more likely to benefit from anti-PD-1/PD-L1 therapies.…”

Section: Tumor Histologymentioning

confidence: 93%

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

et al. 2018

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Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

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“…Though multimodal therapies are often used in patients with non-small cell lung cancer (NSCLC), the overall prognosis of NSCLC remains poor [3]. Immunotherapy is reported to be a relatively effective strategy for NSCLC treatment.…”

Section: Introductionmentioning

confidence: 99%

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

Xie

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. Methods: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and β-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. Results: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3’ UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. Conclusion: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.

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Impact of PD-L1 Expression in Patients with Surgically Resected Non-Small-Cell Lung Cancer

Cited by 37 publications

References 40 publications

Programmed cell death ligand 1 expression in cytologic and surgical non–small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations

Programmed cell death ligand 1 expression in cytologic and surgical non–small cell lung carcinoma specimens from a single institution: Association with clinicopathologic features and molecular alterations

Patient Selection for Anti-PD-1/PD-L1 Therapy in Advanced Non-Small-Cell Lung Cancer: Implications for Clinical Practice

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

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