Circulating Tumour Cells: Detection and Application in Advanced Non-Small Cell Lung Cancer

Andrikou, Kalliopi; Rossi, Tania; Verlicchi, Alberto; Priano, Ilaria; Cravero, Paola; Burgio, Marco Angelo; Crinò, Lucio; Bandini, Sara; Ulivi, Paola; Delmonte, Angelo

doi:10.3390/ijms242216085

Cited by 10 publications

(2 citation statements)

References 120 publications

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“…Nevertheless, new diagnostic tools are needed to measure predictive biomarker expression in NSCLC patients with a view to select individual treatment protocols for them. In line with this, on the one hand, the use of cytology specimens [50,51] and circulating tumor cells [52,53] provides information on the expression of predictive biomarkers, including PD-L1, in NSCLC; on the other hand, the spatial metabolomics approach [54] and lipid profiling [55] can contribute to NSCLC subtyping.…”

Section: Discussionmentioning

confidence: 92%

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-small Cell Lung Cancer

Ufimtseva,

Gileva,

Kostenko

et al. 2024

Preprint

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NSCLC is a very aggressive solid tumor, with a poor prognosis due to post-surgical recurrence. Analysis of the specific tumor and immune signatures of NSCLC samples is a critical step in prognostic evaluation and management decisions for patients after surgery. Routine histological assay has some limitations. Therefore, new diagnostic tools with the capability to quickly recognize NSCLC subtypes and correctly identify various markers are needed. We developed a technique for ex vivo expansion of cancer and immune cells from surgical tumor and lung tissue samples of patients with NSCLC (adenocarcinomas and squamous cell carcinomas) and their examination on ex vivo cell preparations and, parallelly, on histological sections after Romanovsky–Giemsa and immunofluorescent/immunochemical staining for cancer-specific and immune-related markers. As a result, PD-L1 expression was detected for some patients only by ex vivo analysis. Immune cell profiling in the tumor microenvironment revealed significant differences in the immunological landscapes between the patients’ tumors, with smokers’ macrophages with simultaneous expression of pro- and anti-inflammatory cytokines, neutrophils, and eosinophils being the dominant populations. The proposed ex vivo analysis may be used as an additional diagnostic tool for quick examining cancer and immune cells in whole tumor samples and avoiding false negatives in histological assays.

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Section: Discussionmentioning

confidence: 92%

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-small Cell Lung Cancer

Ufimtseva,

Gileva,

Kostenko

et al. 2024

Preprint

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“…The metastatic cascade is a multi-step process, through which tumor cells that slough off the primary tumor travel through the bloodstream and reach other distant organs to develop metastases, which represent the major cause of death in oncologic patients [114,115].…”

Section: Biology and Role In The Metastatic Cascadementioning

confidence: 99%

Extracellular Vesicles, Circulating Tumor Cells, and Immune Checkpoint Inhibitors: Hints and Promises

Bandini,

Ulivi,

Rossi

2024

Cells

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Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of cancer, in particular lung cancer, while the introduction of predictive biomarkers from liquid biopsies has emerged as a promising tool to achieve an effective and personalized therapy response. Important progress has also been made in the molecular characterization of extracellular vesicles (EVs) and circulating tumor cells (CTCs), highlighting their tremendous potential in modulating the tumor microenvironment, acting on immunomodulatory pathways, and setting up the pre-metastatic niche. Surface antigens on EVs and CTCs have proved to be particularly useful in the case of the characterization of potential immune escape mechanisms through the expression of immunosuppressive ligands or the transport of cargos that may mitigate the antitumor immune function. On the other hand, novel approaches, to increase the expression of immunostimulatory molecules or cargo contents that can enhance the immune response, offer premium options in combinatorial clinical strategies for precision immunotherapy. In this review, we discuss recent advances in the identification of immune checkpoints using EVs and CTCs, their potential applications as predictive biomarkers for ICI therapy, and their prospective use as innovative clinical tools, considering that CTCs have already been approved by the Food and Drug Administration (FDA) for clinical use, but providing good reasons to intensify the research on both.

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Combination of circulating tumor cells and 18F‐FDG PET/CT for precision diagnosis in patients with non‐small cell lung cancer

Sun,

Lu,

et al. 2024

Cancer Medicine

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PurposeTo investigate the value of 2‐deoxy‐18f‐fluorodeoxyglucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) and circulating tumor cells (CTCs) for the differential diagnosis of patients with benign lung diseases and those with NSCLC. To explore the phenotypic heterogeneity of CTCs and their correlation with FDG uptake in patients with Stage I–IV NSCLC.MethodsBlood specimens from patients with benign lung diseases and patients with primary NSCLC were collected for the detection of CTCs and their subtypes (epithelial, mixed, and mesenchymal) and analyzed for 18F‐FDG PET/CT tumor metabolic parameters, including the maximum standardized uptake value (SUVmax), standard uptake value (SUL), metabolic tumor volume of primary lesion (MTV), total lesion glycolysis of primary lesion (TLG). Clinical data including age, gender, smoking history, tumor size, TNM stage and pathology type were also collected. The value of the two method alone and in combination for the differential diagnosis of benign and malignant was comparatively analyzed. Finally, the differences in CTC and its subtypes in different stages of NSCLC were compared, and FDG metabolic parameters were correlated with CTC subtypes.ResultsThere were a total of 65 patients with pulmonary diseases, including 12 patients with benign pulmonary diseases and 53 patients with NSCLC. The mean age was 67 ± 10 (38–89 years), 27 were females and 38 were males. 31 (22 males and 9 females) had a long history of smoking. The mean size of the largest diameter of all single lesions was 36 ± 22 mm with a range of 10–108 mm. Seven out of 12 benign diseases were inflammatory granulomatous lesions and 5 were inflammatory pseudotumours. Twenty‐four out of 53 NSCLC were adenocarcinomas and 29 were squamous carcinomas. Twelve out of 53 patients with NSCLC were in Stage I, 10 were in Stage II, 17 were in Stage III and 14 were in Stage IV. SUVmax, SUL, MTV, TLG, total CTCs, epithelial CTCs, and mixed CTCs were all valuable in the differential diagnosis of benign and malignant. TLG combined with mixed CTCs was statistically different from all other diagnostic methods (p < 0.05) and higher than any other diagnostic criteria. In the differential diagnosis of benign and Stage I NSCLC, only total CTC (Z = −2.188 p = 0.039) and mixed CTCs (Z = −3.020 p = 0.014) had certain diagnostic efficacy, and there was no statistical difference between them (p = 0.480). Only mesenchymal CTCs differed in Stage I–IV NSCLC, with a higher number of those who developed distant metastases than those who had non‐distant metastases. Epithelial CTCs correlated with SUVmax (r = 0.333, p = 0.015) and SUL (r = 0.374, p = 0.006). Mmesenchymal CTCs correlated with MTV (r = 0.342, p = 0.018) and TLG (r = 0.319, p = 0.02). Further subgroup analyses revealed epithelial CTCs were correlated with SUVmax (r = 0.543, p = 0.009) and SUL (r = 0.552, p = 0.008), and the total CTCs was correlated with SUVmax (r = 0.622, p = 0.003), SUL (r = 0.652, p = 0.003), MTV (r = 0.460, p = 0.031), and TLG (r = 0.472, p = 0.027) in the early group (Stage I–II). Only mesenchymal CTCs was associated with MTV (r = 0.369, p = 0.041), and TLG (r = 0.415, p = 0.02) in the intermediate‐late group (Stage III–IV).ConclusionBoth FDG PET metabolic parameters and CTCs demonstrated diagnostic value for NSCLC, and combining TLG with mixed CTCs could enhance their diagnostic efficacy. The total CTCs and mixed CTCs showed greater diagnostic value than FDG PET in distinguishing benign lesions from Stage I NSCLC. In NSCLC patients, the epithelial CTCs exhibited a positive correlation with SUVmax and SUL, while mesenchymal CTCs correlated with MTV, and TLG. Besides, epithelial CTCs showed stronger correlations with SUVmax and SUL, and total CTCs showed stronger correlations with SUVmax, SUL, MTV, and TLG in Stage I–II NSCLC. Only mesenchymal CTCs in Stage III–IV NSCLC showed correlations with MTV and TLG. Stage IV NSCLC cases displayed a higher number of mesenchymal CTCs.

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Circulating Tumour Cells: Detection and Application in Advanced Non-Small Cell Lung Cancer

Cited by 10 publications

References 120 publications

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-small Cell Lung Cancer

Development of Ex Vivo Analysis for Examining Cell Composition, Immunological Landscape, Tumor and Immune Related Markers in Non-small Cell Lung Cancer

Extracellular Vesicles, Circulating Tumor Cells, and Immune Checkpoint Inhibitors: Hints and Promises

Combination of circulating tumor cells and 18F‐FDG PET/CT for precision diagnosis in patients with non‐small cell lung cancer

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