Evaluation of PD-L1/PD-1 on circulating tumor cells in patients with advanced non-small cell lung cancer

Kallergi, Galatea; Vetsika, Eleni-Kyriaki; Aggouraki, Despoina; Lagoudaki, Eleni; Koutsopoulos, Anastasios; Koinis, Filippos; Katsarlinos, Panagiotis; Trypaki, Maria; Messaritakis, Ippokratis; Stournaras, Christos; Georgoulias, Vassilis; Κotsakis, Athanasios

doi:10.1177/1758834017750121

Cited by 63 publications

(65 citation statements)

References 45 publications

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“…Similar findings were observed by Guibert et al in NSCLC, where PD‐L1+ CTCs were seen in all patients at progression. Moreover, the presence of high PD‐L1+ CTCs associated with a poorer patient outcome . While outside the scope of this study, longitudinal blood sampling after treatment could give important insights into the role/persistence of PD‐L1‐positive CTCs .…”

Section: Discussionmentioning

confidence: 95%

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

et al. 2018

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Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD‐L1) CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23 (47.8%) of head and neck cancer (HNC) patients and 17/33 (51.5%) of non‐small‐cell lung cancer (NSCLC) patients. CTCs were determined to be PD‐L1‐positive in 6/11 (54.4%) HNC and 11/17 (64.7%) NSCLC cases, respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC‐positive patients had shorter progression‐free survival (PFS) (hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571‐15.57; P = 0.0063), and PD‐L1‐positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011‐26.33; P = 0.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246; 95% [CI]:0.9565‐5.273; P = 0.0632), nor the presence of PD‐L1 expression ([HR]:1.646; 95% [CI]:0.5128‐5.283; P = 0.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them.

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Section: Discussionmentioning

confidence: 95%

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

et al. 2018

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“…The evaluation of PD-L1 expression on CTCs has been assessed in different solid tumors including lung [66,[78][79][80][81][82][83][84], bladder [85], breast [86], HNSCC [87,88], colon [84,89] and prostatic carcinoma [84,89] (Table 2). Independently of the technical issues cited above, other challenges rapidly emerged: (i) is PD-L1 expressed on all CTCs or only in a subpopulation of CTCs?…”

Section: Analysis Of the Expression Of Pd-l1 In Ctcsmentioning

confidence: 99%

Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients?

2019

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The emergence of immunotherapy in oncology requires the discovery, validation and subsequent adoption of robust, sensitive and specific predictive and prognostic biomarkers for daily practice. Until now, anti-PD-L1 immunohistochemistry (IHC) on tissue sections has been the only validated companion diagnostic test for first-line immunotherapy for advanced and metastatic cancer, notably non-small-cell lung cancer (NSCLC). However, detection of this biomarker presents limitations that have stimulated the development of other biomarkers and other approaches. Within this context, the use of a liquid biopsy (LB) could provide an important complementary or alternative added value to PD-L1 IHC. In this review, we discuss how LBs have been used in the field of immuno-oncology (I-O) to predict response, relapse or adverse advents for patients undergoing immune-checkpoint inhibitor (ICI) therapy (anti-PD-1/PD-L1 and CTLA-4) and we highlight recent developments. Circulating tumor cells (CTCs), cell-free DNA (cfDNA), proteins and cytokines detected in plasma as well as circulating T-lymphocytes are discussed as potential sources for developing new I-O biomarkers. The quantification of cfDNA as a predictive biomarker, as well as its sequencing for the determination of tumor mutational burden, is already well advanced. Additionally, the quantification of PD-L1 from CTCs, bound on exosomes or free in plasma, as well as the determination of cytokines, are also being actively investigated with promising results having recently been published. Lastly, analysis of T-lymphocytes, especially by analyzing the T-cell receptor, has recently emerged as a valuable biomarker that might become relevant for the prediction of response to ICIs. While LBs have not yet been implemented in routine I-O clinical practice, recent promising data and rapidly advancing technologies indicate that this approach has the potential to soon personalize the clinical management of cancer patients receiving ICIs.

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“…Using the CELLSEARCH system and ISET filtration platform, it has been reported that PD-L1-positive CTCs were detected in 8% to 95% of CTCs. [17][18][19][20] The differences in the PD-L1 positivity rate may result from several reasons, such as different platforms for CTC detection, different antibodies for PD-L1 staining, and different patient populations at the different time points. Ilie et al reported that concordance rate for PD-L1 positivity between tissue and CTCs was 93%, 18 which is different from our findings.…”

Section: Pd-l1-expressing Ctcs In Lung Cancermentioning

confidence: 99%

“…21 Another report using the ISET filtration system showed a different PD-L1 positivity rate (53%), and this may also result from the usage of a different antibody (clone EH 12.2H7). 20 A few studies have been conducted to evaluate the predictive significance of PD-L1-positive CTCs for the treatment with immune checkpoint inhibitors in patients with lung cancer. Nicolazzo et al assessed the predictive significance of PD-L1-positive CTCs for treatment with nivolumab and reported that baseline PD-L1positive CTCs at least did not correlate with the clinical benefit, although they reported the significance of longitudinal monitoring.…”

Section: Pd-l1-expressing Ctcs In Lung Cancermentioning

confidence: 99%

Heterogeneous Expression of Programmed Death Receptor-ligand 1 on Circulating Tumor Cells in Patients With Lung Cancer

Koh

Yagi

Akamatsu

et al. 2019

Clinical Lung Cancer

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Circulating tumor cells (CTCs) and their programmed death receptor-ligand 1 (PD-L1) expression in patients with lung cancer were detected using a microcavity array system. PD-L1 expression was detected in 73% of patients who harbored CTCs. The proportion of PD-L1-positive CTCs ranged from 3% to 100%, suggesting intra-patient heterogeneity. No correlation on PD-L1 expression was observed between tumor tissues and CTCs. Background: Blockade of the programmed death receptor-1 (PD-1) pathway is effective against solid tumors including lung cancer. PD-ligand 1 (PD-L1) expression on tumor tissue serves as a predictive biomarker for the efficacy of PD-1 pathway blockade. Here, we evaluated the expression of PD-L1 on circulating tumor cells (CTCs) in patients with lung cancer. Materials and Methods: Peripheral whole blood (3 mL) was collected from patients, and CTCs and PD-L1 expression were detected using a microcavity array (MCA) system. Immunohistochemistry for PD-L1 detection was also performed using matched tumor tissues. Results: Sixty-seven patients with lung cancer were enrolled in the study between July 2015 and April 2016 at Wakayama Medical University Hospital. The characteristics of the patients were as follows: median age, 71 years (range, 39-86 years); male, 72%; stage II to III/IV, 14%/85%; nonesmall-cell lung cancer/small-cell lung cancer/other, 73%/21%/6%. CTCs were detected in 66 of 67 patients (median, 19; range, 0-115), and more than 5 CTCs were detected in 78% of patients. PD-L1-expressing CTCs were detected in 73% of patients, and the proportion score of PD-L1-expressing CTCs ranged from 3% to 100%, suggesting intra-patient heterogeneity of PD-L1 expression on CTCs. Tumor tissues were available from 27 patients and were immunostained for PD-L1, and no correlation was observed between tumor tissues and CTCs based on the proportion score (R 2 ¼ 0.0103). Conclusion: PD-L1 expression was detectable on CTCs in patients with lung cancer, and intra-patient heterogeneity was observed. No correlation was observed between PD-L1 expression in tumor tissues and CTCs.

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Evaluation of PD-L1/PD-1 on circulating tumor cells in patients with advanced non-small cell lung cancer

Cited by 63 publications

References 45 publications

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

Liquid biopsy in the era of immuno-oncology: is it ready for prime-time use for cancer patients?

Heterogeneous Expression of Programmed Death Receptor-ligand 1 on Circulating Tumor Cells in Patients With Lung Cancer

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