Heterogeneity and prognosis of programmed cell death-ligand 1 expression in the circulating tumor cells of non-small cell lung cancer

Wang, Helin; Wu, Jieqing; Wáng, Ying; Yu, Jian; Mao, Xiaona; Li, Zhuoran; Huang, Niu; Jin, Cailing; Wang, Xiao-Jue; Yan, Zhengcun; Yi, Ling; Yang, Bin; Wei, Panjian; Zhang, Hongtao; Zhang, Shucai

doi:10.4149/neo_2021_210115n67

Cited by 4 publications

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“…The presence of PD-L1 + CTCs in previous reports has either been associated with significantly worse OS [ 30 , 42 ], PFS [ 40 ], or disease-free survival (DFS) compared to patients having PD-L1 − CTCs [ 35 ]. However, in other studies, the presence of PD-L1 + CTCs was associated with only a trend for worse PFS [ 16 , 30 ], which was not statistically significant, or even no correlation at all with PFS [ 11 , 32 , 38 , 43 ] or OS [ 11 , 32 , 35 , 38 , 41 ]. On two occasions, the presence of PD-L1 + CTCs was associated with longer PFS and/or OS [ 34 , 41 ].…”

Section: Discussionmentioning

confidence: 85%

“…CTC positivity in NSCLC, whether CTCs have been identified by label-dependent or -independent methods and irrespective of treatment regime, has been reported to range between approx. 43–100%, with the ISET technology showing far better detection ability and recovery [ 3 , 11 , 14 , 16 , 17 , 18 , 19 , 30 , 32 , 34 , 35 , 36 , 37 , 38 , 39 ]. Therefore, in the current study, ISET technology has been used for the isolation of CTCs.…”

Section: Discussionmentioning

confidence: 99%

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PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

et al. 2022

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The PD-1/PD-L1 axis provides CTCs an escape route from the immune system. Phosphorylation of the ribosomal protein S6 is implicated in the same pathway, following mTOR activation. The aim of the study was to investigate the expression of PD-L1 and pS6 in CTCs from NSCLC patients under Osimertinib treatment at a single cell level. CTCs were isolated using ISET from NSCLC patients’ blood [37 at baseline, 25 after the 1st cycle, and 23 at the end of treatment (EOT)]. Staining was performed using immunofluorescence. Cytokeratin-positive (CK+) CTCs were detected in 62% of patients. CK+PD-L1+CD45− and CK+pS6+ phenotypes were detected in 38% and 41% of the patients at baseline, in 28% and 32% after 1st cycle, and in 30% and 35% at EOT, respectively. Spearman’s analysis revealed statistically significant correlations between PD-L1 and pS6 phenotypes at all time points. Survival analysis revealed that CK+pS6+ (p = 0.003) and CKlowpS6+ (p = 0.021) phenotypes after 1st cycle were related to significantly decreased one-year progression-free survival (PFS12m) and PFS, respectively. CK+PD-L1+CD45−phenotype at baseline and after 1st cycle showed a trend for decreased PFS12m. Increased expression of PD-L1/pS6 in CTCs of Osimertinib-treated NSCLC patients implies the activation of the corresponding pathway, which is potentially associated with poor clinical outcomes.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

et al. 2022

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“…A total of 11 studies with 472 patients were included in our meta-analysis. Five studies 16–20 were mainly from Asia, and 6 21–25 contained a large European population. Five studies 16–19,24 included patients with all stages of lung cancer, and 6 20–23,25 included only patients with advanced lung cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Five studies 16–20 were mainly from Asia, and 6 21–25 contained a large European population. Five studies 16–19,24 included patients with all stages of lung cancer, and 6 20–23,25 included only patients with advanced lung cancer. Patients in 7 of the studies were new patients, 16–21,24 while patients in 4 of the studies were previously treated.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic value of programmed cell death-ligand 1 expression on circulating tumor cells in lung cancer: A systematic review and meta-analysis

Cui,

Wan,

Yang

et al. 2023

Int J Biol Markers

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Background The expression of programmed cell death-ligand 1 (PD-L1) on circulating tumor cells offers a noninvasive method for the detection of PD-L1 expression in lung cancer, and could serve as a potential surrogate for cancer tissue. However, discrepant results make it difficult to apply PD-L1 on circulating tumor cells to clinical practice. Therefore, we conducted a meta-analysis to investigate the diagnostic value of PD-L1 on circulating tumor cells in lung cancer. Methods To identify the relationship between the expression of PD-L1 on circulating tumor cells and lung cancer, the PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched from inception to March 2023. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the corresponding 95% confidence intervals were calculated to assess the diagnostic performance of PD-L1. We also conducted subgroup and sensitivity analyses. Results A total of 11 studies including 472 lung cancer patients were included in our study. The overall performance in terms of pooled sensitivity and specificity was 0.72 (0.52–0.86) and 0.54 (0.25–0.81), respectively. The positive likelihood ratio, negative likelihood ratio, and area under the curve were 1.57 (0.87–2.84), 0.52 (0.30–0.90), and 0.70 (0.66–0.74), respectively. Deeks’ funnel plot test indicated no publication bias. Conclusion Our analysis demonstrated that positive PD-L1 expression on circulating tumor cells (CTCs) exhibited a moderate diagnostic value in lung cancer, and CTCs may serve as a feasible alternative tissue analysis for the detection of PD-L1 in lung cancer.

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“…To our knowledge, this study is the first report characterizing OSCC clonal evolution from the normal mucosa status to the primary carcinoma stage and metastatic stage in a mouse model. CD326 immunomagnetic bead sorting was frequently used for enriching tumor cells in peripheral blood of lung cancer and esophageal cancer [30,31]. The detection rate of tumor cells in peripheral blood was improved from nearly undetectable to more than 24.14% by using CD45 and CD326 immunomagnetic beads [32].…”

Section: Discussionmentioning

confidence: 99%

Temporal and spatial characteristics of tumor evolution in a mouse model of oral squamous cell carcinoma

Cao

Dong

et al. 2022

BMC Cancer

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Objectives We aimed to elucidate the temporal and spatial characteristics of tumor evolution in an oral squamous cell carcinoma (OSCC) mouse model with higher burden of lymphatic metastasis through high-throughput sequencing. Methods The OSCC model was established in 9 mice. DNA was extracted from the tumors of primary tongue lesions and disseminated tumor cells (DTCs) of submandibular gland lymph nodes and bone marrow, and then whole genome sequencing was performed. After bioinformatics analysis, somatic single-nucleotide variants (SSNVs) and copy number variations (CNVs) data were obtained. Based on SSNVs, clonal architecture and ancestor-descendant relationships among tumor cell subclones were elucidated. Results A total of 238 tumor-related SSNVs with 120 high-frequency mutated genes were obtained from 36 samples of 9 mice by whole-genome sequencing. The number of unique SSNVs in the primary lesion, submandibular lymph node and bone marrow was greater than the number of shared SSNVs. Furthermore, the primary lesion-originated subclones, which were identified by SSNVs, were also detected in submandibular lymph nodes in the early stage of oral carcinogenesis. Moreover, at different histopathological stages, unique subclones were also identified in DTCs isolated from lymph nodes. Conclusion Tumor heterogeneity is significant in primary tumor cells and disseminated tumor cells. OSCC cells probably disseminate to lymph nodes in the early stage of oral carcinogenesis. OSCC is characterized by polyclonal dissemination, and the evolutionary trajectory of DTCs is potentially dominated by the tumor microenvironment.

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Heterogeneity and prognosis of programmed cell death-ligand 1 expression in the circulating tumor cells of non-small cell lung cancer

Cited by 4 publications

References 0 publications

PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

PD-L1/pS6 in Circulating Tumor Cells (CTCs) during Osimertinib Treatment in Patients with Non-Small Cell Lung Cancer (NSCLC)

Diagnostic value of programmed cell death-ligand 1 expression on circulating tumor cells in lung cancer: A systematic review and meta-analysis

Temporal and spatial characteristics of tumor evolution in a mouse model of oral squamous cell carcinoma

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