PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non–small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Dall’Olio, Filippo Gustavo; Gelsomino, Francesco; Conci, Nicole; Marcolin, Laura; Giglio, Andrea De; Grilli, Giada; Sperandi, Francesca; Fontana, Francesca; Terracciano, Mario; Fragomeno, Benedetta; Tober, Nastassja; Manferrari, Giulia; Brocchi, Stefano; Golfieri, Rita; Fiorentino, Michelangelo; Ardizzoni, Andrea

doi:10.1016/j.cllc.2021.03.005

Cited by 45 publications

(37 citation statements)

References 36 publications

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“…There is a satisfactory correlation between PD-L1 expression on tumoral cells and patients’ response to immune checkpoint inhibitors. The level of PD-L1 expression on circulating tumor cells (CTCs) is also considered a favorable biomarker in patients treated with ICIs, at least in the cases of NSCLC and melanoma [ 11 , 12 , 13 ]. PD-L1 expressed on CTCs is also viewed as a useful biomarker for the early detection of cancers [ 14 ].…”

Section: The Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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Upon T-cell receptor stimulation, the Programmed cell Death-1 receptor (PD-1) expressed on T-cells can interact with its ligand PD-L1 expressed at the surface of cancer cells or antigen-presenting cells. Monoclonal antibodies targeting PD-1 or PD-L1 are routinely used for the treatment of cancers, but their clinical efficacy varies largely across the variety of tumor types. A part of the variability is linked to the existence of several forms of PD-L1, either expressed on the plasma membrane (mPD-L1), at the surface of secreted cellular exosomes (exoPD-L1), in cell nuclei (nPD-L1), or as a circulating, soluble protein (sPD-L1). Here, we have reviewed the different origins and roles of sPD-L1 in humans to highlight the biochemical and functional heterogeneity of the soluble protein. sPD-L1 isoforms can be generated essentially by two non-exclusive processes: (i) proteolysis of m/exoPD-L1 by metalloproteases, such as metalloproteinases (MMP) and A disintegrin and metalloproteases (ADAM), which are capable of shedding membrane PD-L1 to release an active soluble form, and (ii) the alternative splicing of PD-L1 pre-mRNA, leading in some cases to the release of sPD-L1 protein isoforms lacking the transmembrane domain. The expression and secretion of sPD-L1 have been observed in a large variety of pathologies, well beyond cancer, notably in different pulmonary diseases, chronic inflammatory and autoimmune disorders, and viral diseases. The expression and role of sPD-L1 during pregnancy are also evoked. The structural heterogeneity of sPD-L1 proteins, and associated functional/cellular plurality, should be kept in mind when considering sPD-L1 as a biomarker or as a drug target. The membrane, exosomal and soluble forms of PD-L1 are all integral parts of the highly dynamic PD-1/PD-L1 signaling pathway, essential for immune-tolerance or immune-escape.

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Section: The Pd-1/pd-l1 Checkpointmentioning

confidence: 99%

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Bailly

Thuru

Quesnel

2021

Cancers

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“…Furtherly, we excluded five candidate studies for the following reasons: one only provided specimen‐level survival data, 29 one reported the correlation of PD‐L1 + CTCs/circulating immune cells with survival, 30 one was duplicated with another study, 18 , 31 and two did not report survival outcomes. 32 , 33 Finally, we identified 30 studies eligible for the present meta‐analysis 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 as shown in Figure 1 . A total of 1419 patients with malignant tumors, including 208 breast cancer, 253 gastrointestinal cancer, 194 genitourinary cancer, 161 head and neck cancer, 25 melanoma, 12 metastatic neuroendocrine tumor, and 566 NSCLC, were analyzed.…”

Section: Resultsmentioning

confidence: 99%

“… 18 In NSCLC patients receiving ICI treatment, PD‐L1 + CTCs were associated with better PFS and OS. 53 However, some studies did not find a significant association between PD‐L1 + CTCs and survival for ICI treatment. 38 , 48 , 49 Subgroup meta‐analysis by pooling these studies together showed that patients having PD‐L1 + CTCs and treated with PD‐1/PD‐L1 inhibitors may have prolonged PFS (HR = 0.55, 95% CI 0.28–1.08) and OS (HR = 0.61, 95% CI 0.36–1.04).…”

Section: Discussionmentioning

confidence: 99%

“…Furtherly, we excluded five candidate studies for the following reasons: one only provided specimen-level survival data, 29 one reported the correlation of PD-L1 + CTCs/circulating immune cells with survival, 30 one was duplicated with another study, 18,31 and two did not report survival outcomes. 32,33 Finally, we identified 30 studies eligible for the present meta-analysis [18][19][20][21][22][23][24][25][26][27][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] as shown in Figure 1…”

Section: Baseline Features Of Eligible Studiesmentioning

confidence: 99%

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Prognostic significance of programmed cell death‐ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta‐analysis

et al. 2021

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“…At present, immunotherapy drugs for lung cancer are mainly immune checkpoint inhibitors, such as programmed cell death protein-1 / programmed cell death ligand 1(PD-1 / PD-L1) [9]. A number of large-scale clinical trials have shown that compared with chemotherapy patients, the overall survival of lung cancer patients treated with PD-1 / PD-L1 immune checkpoint inhibitors is significantly longer [10,11]. Although technological progress has improved the diagnosis and treatment of LUAD, the 5-year survival rate is only 10-15% [12].…”

Section: Introductionmentioning

confidence: 99%

Downregulation of CENPK suppresses lung adenocarcinoma by regulating EMT

2021

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IntroductionCentromere protein K (CENPK) plays a key role in regulating the assembly and function of centromeres, which in turn can affect the occurrence and development of various tumors. However, little is known about the biological function of CENPK in lung adenocarcinoma (LUAD).Material and methodsWe analyzed the relationship between CENPK expression and the clinicopathological characteristics of LUAD patients via bioinformatics methods. Then, the role of CENPK in LUAD was investigated in vitro by using the human LUAD cell line A549.The cell counting kit-8 and colony formation assays were used detect the cell proliferation ability. The wound healing and transwell assays were used to detect the cell migration and invasion ability. The epithelial-mesenchymal transition (EMT) markers (E-cadherin, N-cadherin, Snail and Vimentin) were measured by western blotting.ResultsCENPK is highly expressed in LUAD tissues and cell lines. Moreover, high expression of CENPK in LUAD is significantly associated with stage, lymph node involvement and poor survival. CENPK knockdown significantly decreases the proliferation, migration and invasion ability of A549 cells by regulating epithelial-mesenchymal transition (EMT).ConclusionsCENPK is highly expressed in LUAD and leads to a poor prognosis. CENPK knockdown can suppress the proliferation, migration, and invasion of lung cancer cells via EMT, which may be a valid target for treatment.

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PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non–small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Cited by 45 publications

References 36 publications

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Soluble Programmed Death Ligand-1 (sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases

Prognostic significance of programmed cell death‐ligand 1 expression on circulating tumor cells in various cancers: A systematic review and meta‐analysis

Downregulation of CENPK suppresses lung adenocarcinoma by regulating EMT

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