Clinicopathological and molecular characteristics associated with PD-L1 expression in non-small cell lung cancer: a large-scale, multi-center, real-world study in China

Zheng, Qiang; Huang, Yan; Zeng, Xin; Chen, Xiaoyan; Shao, Shihong; Jin, Yan; Xue, Qianqian; Wang, Yue; Guo, Yan; Gu, Bin; Wu, Chunyan; Li, Yuan

doi:10.1007/s00432-020-03444-y

Cited by 24 publications

(28 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tsao et al [30] found a higher expression of PD-L1 in poorly differentiated early-stage NSCLC samples, including large cell, adenosquamous, pleomorphic and sarcomatoid carcinomas. The study by Hong et al [29] observed a higher expression of PD-L1 in squamous cell carcinomas than adenocarcinomas, while the study recently published by Zheng and colleagues [31] found a higher positivity of PD-L1 in squamous cell carcinomas and other histological subtypes of NSCLC compared to adenocarcinomas. Nonetheless, these results seem controversial, as other studies have not found these differences [32], or have reported higher staining in adenocarcinomas [33].…”

Section: Discussionmentioning

confidence: 93%

“…Gagne et al [32] found a greater PD-L1 expression in cell blocks compared to biopsies and surgical specimens, but supporting our findings, a higher proportion of PD-L1 TPS ≥ 50% was found in biopsies compared with surgical specimens. Along these lines, Zheng et al [31] found that PD-L1 expression was higher in biopsies than in surgically resected specimens in a real-world study in China. The discrepancy found between PD-L1 expression in biopsy compared to resection specimens could be due to intratumoral heterogeneity, an advanced stage of the biopsy samples compared to the surgical specimens or the age of the samples.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain

et al. 2021

View full text Add to dashboard Cite

Anti-programmed cell death (PD1)/ligand-1 (PD-L1) checkpoint inhibitors have improved the survival of non-small cell lung cancer (NSCLC) patients. Additionally, PD-L1 has emerged as a predictive biomarker of response. Our goal was to examine the histological features of all PD-L1 cases of NSCLC analyzed in our center between 2017 and 2020, as well as to correlate the expression values of the same patient in different tested samples. PD-L1 immunohistochemistry (IHC) was carried out on 1279 external and internal samples: 482 negative (tumor proportion score, TPS < 1%; 37.7%), 444 low-expression (TPS 1–49%; 34.7%) and 353 high-expression (TPS ≥ 50%; 27.6%). Similar results were observed with samples from our institution (N = 816). Significant differences were observed with respect to tumor histological type (p = 0.004); squamous carcinoma was positive in a higher proportion of cases than other histological types. There were also differences between PD-L1 expression and the type of sample analyzed (surgical, biopsy, cytology; p < 0.001), with a higher frequency of negative cytology. In addition, there were cases with more than one PD-L1 determination, showing heterogeneity. Our results show strong correlation with the literature data and reveal heterogeneity between tumors and samples from the same patient, which could affect eligibility for treatment with immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 95%

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This assay was performed on the Dako Autostainer Link 48 platform according to an automated staining protocol. The specific steps of PD‐L1 IHC staining were performed as described previously 29,30 . Briefly, we followed the manufacturer's protocol for the Dako system and used the Dako clone 22C3 assay on the Dako Link 48 automated platform.…”

Section: Methodsmentioning

confidence: 99%

“…The specific steps of PD‐L1 IHC staining were performed as described previously. 29 , 30 Briefly, we followed the manufacturer's protocol for the Dako system and used the Dako clone 22C3 assay on the Dako Link 48 automated platform. Each analysis of PD‐L1 was developed with both paired Dako positive and negative controls (cell line).…”

Section: Methodsmentioning

confidence: 99%

Association of the programmed death ligand‐1 combined positive score in tumors and clinicopathological features in esophageal cancer

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background The combined positive score (CPS) of the programmed death ligand‐1 (PD‐L1) 22C3 assay is a predictive marker of pembrolizumab monotherapy for advanced esophageal cancer (EC) patients. However, little is known about the association of the PD‐L1 22C3 CPS with the clinicopathological features and heterogeneity of PD‐L1 expression in EC in the Chinese population in a real‐world setting. Methods We examined the association of the PD‐L1 22C3 CPS with clinicopathological characteristics in 533 EC specimens. Further, we compared 37 cases' different blocks of the same specimen and 50 paired primary/metastatic lymph node lesions to investigate the heterogeneity of PD‐L1 expression. Results PD‐L1 positive expression was observed in 45.0% of 533 EC patients, including 46.8% with squamous cell carcinoma, 15.4% with adenocarcinoma, 28.6% with basaloid squamous carcinoma, 42.9% with spindle cell carcinoma, and 33.3% with neuroendocrine tumors. PD‐L1 positive expression was positively associated with lymph node metastasis (59.2% chance, p = 0.021) and venous/lymphatic invasion (66.3% chance, p = 0.029). PD‐L1 expression was highly consistent in different paraffin blocks of the same surgically resected specimen (concordance rate: 86.5%, p = 0.000016) and a moderate consistency (concordance rate: 78.0%, p = 0.000373) for the primary and metastatic lymph node lesion comparison. Conclusions This is a novel study which demonstrated a positive correlation between a high PD‐L1 22C3 CPS and invasion/metastasis risk in EC surgical specimens. Both paired blocks and paired primary/metastatic lymph node lesions showed significant concordance. PD‐L1 heterogeneity was inferred to be mainly related to positive mononuclear inflammatory cells (MICs), which might have substantial implications for clinical practice.

show abstract

“…The relationship between PD-L1/PD-1 expression levels and EGFR mutation status, as well as the interaction between the PD-1/PD-L1 and EGFR pathways, are poorly understood (56,(103)(104)(105)(106). Notably, a large−scale, multicenter, real−world study in China identified a significant association between PD-L1 expression levels and EGFR mutation and ALK rearrangement (107). Future Chinese studies are critical to addressing this issue given the higher EGFR mutation rates in Chinese patients with NSCLC compared with their Western counterparts (approximately 28% in unselected Chinese patients with NSCLC vs. 17% in Western populations) (28,108,109).…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

2021

View full text Add to dashboard Cite

Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the predominant type of lung cancer, accounting for approximately 80%–85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.

show abstract

Clinicopathological and molecular characteristics associated with PD-L1 expression in non-small cell lung cancer: a large-scale, multi-center, real-world study in China

Cited by 24 publications

References 28 publications

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain

PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain

Association of the programmed death ligand‐1 combined positive score in tumors and clinicopathological features in esophageal cancer

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

Contact Info

Product

Resources

About