Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases

Uruga, Hironori; Bozkurtlar, Emine; Huynh, Tiffany G.; Muzikansky, Alona; Goto, Yasushi; Gomez‐Caraballo, María; Hata, Aaron N.; Gainor, Justin F.; Mark, Eugene J.; Engelman, Jeffrey A.; Lanuti, Michael; Mino‐Kenudson, Mari

doi:10.1016/j.jtho.2016.10.015

Cited by 109 publications

(92 citation statements)

References 39 publications

(60 reference statements)

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“…In our study, we enrolled 117 LUAD patients who were diagnosed as "pan-negative" by excluding common mutations and translocations, and 104 LUAD patients who harbored one of the six gene aberrations mentioned above. It was interesting that both pan-negative and mutant patients presented low PD-L1 expression, which was significantly different from the high PD-L1 expression rate reported in previous studies (6)(7)(8)15). This result indicates that LUAD patients in East Asian population may not benefit from immunotherapy.…”

Section: Discussioncontrasting

confidence: 81%

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Pan

Zheng

et al. 2017

J. Thorac. Dis.

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Background: To determine the proportion and clinical features of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer (NSCLC).Methods: PD-L1 expression was assessed by immunohistochemistry (IHC) and tumor proportion score (TPS) with the use of PD-L1 IHC 22C3 antibody (Dako North America) in 108 surgically resected lung squamous cell carcinomas (SCC) and 221 lung adenocarcinomas (LUADs), and was correlated with clinical variables, histologic subtypes, and common driver mutations.Results: Positive PD-L1 expression was found in 37 lung SCC (37/108, 34.3%), including 15 cases with TPS ≥50% (15/108, 13.9%) and 22 cases with TPS <50% (22/108, 20.4%). In adenocarcinoma cohort, 9 cases were found PD-L1 expression positive (9/221, 4.1%), including 1 case with TPS ≥50% (1/221, 0.5%) and 8 cases with TPS <50% (8/221, 3.9%). Totally, high PD-L1 expression (TPS ≥50%) was significantly associated with male sex (P=0.026), current/ever smoking history (P=0.008) and SCC subtype (P<0.001).Positive PD-L1 expression (including TPS ≥50% and TPS <50% ) in LUAD cohort was significantly associated with male sex (P=0.046), current/ever smoking history (P=0.002), mutation pan-negative status (P=0.038), solid-predominant subtype (P<0.001), large tumor size (P=0.027) and lymph node metastasis (P=0.019). No significant difference was found between PD-L1 high expression group (TPS ≥50%) and low/ negative expression group in SCC cohort.Conclusions: This study revealed the unique distribution of PD-L1 expression in East Asian NSCLCs, which is largely different from Western populations. Since the high response rate of pembrolizumab in the treatment of lung cancer patients with PD-L1 TPS ≥50%, this result indicates that prospective PD-L1 expression testing in specific East Asian patients could facilitate decision making for immunotherapy.

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Section: Discussioncontrasting

confidence: 81%

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Pan

Zheng

et al. 2017

J. Thorac. Dis.

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“…7,[28][29][30] However, PD-L1 expression might differ between primary tumor and metastases as described for renal cell carcinoma and lung adenocarcinoma. [31][32][33] Therefore, it must be pointed out that a majority (57%) of tumor samples in our study was from metastatic sites, while previous studies in PC determined PD-L1 expression in the pancreatic primary. 7,[27][28][29][30] In lymphoma patients, levels of sPD-L1 have been reported to be independent of tumoral PD-L1 expression.…”

Section: Discussionmentioning

confidence: 76%

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

et al. 2017

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Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet.In contrast to other tumor entities, sPD-1/sPD-L1 levels did not indicate an adverse outcome in a cohort of 41 patients with advanced PC. We observed a close positive correlation of sPD-L1 levels with sPD-1 in patients with advanced PC, suggesting a common provenience and regulation of sPD-1 and sPD-L1 in cancer patients. Higher sPD-L1 levels were present in patients with elevated C-reactive protein or strong tumoral T cell infiltration, while no correlation of sPD-L1 levels with tumoral PD-L1 expression was found. Our findings indicate that sPD-1 and sPD-L1 are markers of systemic inflammation in (pancreatic) cancer. In a subset of PC patients, elevation in sPD-L1 levels might be caused by an inflammatory tumor typeindependent of tumoral PD-L1 expression.

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“…For example, some studies have demonstrated heterogeneity between microarray cores from the same block, whereas others have shown that although heterogeneity exists between different parts of a tumor, tumor within a single block is relatively homogeneous . In addition, 2 recent studies have demonstrated discrepancies in PD‐L1 expression between primary tumors and lymph node metastases in 30% to 38% of NSCLC cases, suggesting that tumor heterogeneity may affect PD‐L1 assessment of a tumor at different anatomical sites . The results of these studies led us to investigate whether there was a difference in the correlation of PD‐L1 expression between surgical samples and cytology samples collected from different anatomical sites compared with cytology samples collected from the same site.…”

Section: Discussionmentioning

confidence: 99%

Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

Russell‐Goldman

Kravets

Dahlberg

et al. 2018

Cancer Cytopathology

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Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases

Cited by 109 publications

References 39 publications

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

Cytologic‐histologic correlation of programmed death‐ligand 1 immunohistochemistry in lung carcinomas

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