Circulating Factors—CAMLs, CTC/cfDNA—Predictive Factors to Aid in Diagnoses of Cancer and Determination of Its Recurrence

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 8146

Special Issue Editor


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Guest Editor
Fox Chase Cancer Center, Philadelphia, PA 19111, USA
Interests: CTC (circulating tumor cells); CAMLs (cancer associated macrophage like); cfDNA (cell free DNA); predictive factors; response to treatment; progression of disease

Special Issue Information

Dear Colleagues,

Evaluable biological specimens within circulation can aid in diagnosing the presence, progression or steady state of a malignancy and are fundamental in determining whether a cancer treatment is effective. Circulating cells and liquid components that are indicators of the presence of a malignancy have been identified in blood. Cellular components include cancer-associated macrophage-like cells (CAMLs). CAMLs are enlarged phagocytic macrophage-like cells ranging from 30 to 300 mm in length that stain positive for CD14 and CD45 with internal markers staining for endothelial cells, tumor/normal cells and fibroblasts. Tissue macrophages engulf and clear both dying and damaged normal cells, malignant cells and cell fragments from the body. Macrophages, via immunologic self-recognition of epitopes, have the ability to determine whether these cells are self or mutated. As a tumor advances, macrophages become larger. A second cell is an intact circulating tumor cell (CTC) that has detached from a tumor, entered lymphatic flow and emptied into the blood circulation. CTC testing is currently approved as a clinical test for breast, prostate and colorectal cancers. In addition to these cells, cell-free DNA is a blood component resulting both from normal and malignant cells. Cell-free DNA requires a base concentration to be detected and be able to differentiate tumor from normal DNA. Prior to treatment or at progression, the values of these components will vary with response to treatment, steady-state (non-progression but still the presence of a malignancy) and response to treatment. All three of these biological entities are capable of being informative regarding the status of a tumor and can be used to identify which mutations are active in the current malignancy. Combining CAML, CTC and cfDNA analyses as a strategy for screening high-risk populations has the potential to identify and treat patients in early stage disease, where it can have the greatest impact.

Dr. Katherine Alpaugh
Guest Editor

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Keywords

  • CAMLs
  • CTC
  • cfDNA
  • high risk testing
  • cancer screening
  • treatment surveillance
  • tumor status
  • active mutations

Published Papers (4 papers)

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Research

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19 pages, 1987 KiB  
Article
Extracellular Vesicles’ Genetic Cargo as Noninvasive Biomarkers in Cancer: A Pilot Study Using ExoGAG Technology
by Carolina Herrero, Alba Ferreirós, Daniel Pérez-Fentes, Luis León-Mateos, Rafael López-López, Miguel Abal and Lorena Alonso-Alconada
Biomedicines 2023, 11(2), 404; https://doi.org/10.3390/biomedicines11020404 - 30 Jan 2023
Viewed by 2278
Abstract
The two most developed biomarkers in liquid biopsy (LB)—circulating tumor cells and circulating tumor DNA—have been joined by the analysis of extracellular vesicles (EVs). EVs are lipid-bilayer enclosed structures released by all cell types containing a variety of molecules, including DNA, mRNA and [...] Read more.
The two most developed biomarkers in liquid biopsy (LB)—circulating tumor cells and circulating tumor DNA—have been joined by the analysis of extracellular vesicles (EVs). EVs are lipid-bilayer enclosed structures released by all cell types containing a variety of molecules, including DNA, mRNA and miRNA. However, fast, efficient and a high degree of purity isolation technologies are necessary for their clinical routine implementation. In this work, the use of ExoGAG, a new easy-to-use EV isolation technology, was validated for the isolation of EVs from plasma and urine samples. After demonstrating its efficiency, an analysis of the genetic material contained in the EVs was carried out. Firstly, the sensitivity of the detection of point mutations in DNA from plasma EVs isolated by ExoGAG was analyzed. Then, a pilot study of mRNA expression using the nCounter NanoString platform in EV-mRNA from a healthy donor, a benign prostate hyperplasia patient and metastatic prostate cancer patient plasma and urine samples was performed, identifying the prostate cancer pathway as one of the main ones. This work provides evidence for the value of using ExoGAG for the isolation of EVs from plasma and urine samples, enabling downstream applications of the analysis of their genetic cargo. Full article
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11 pages, 912 KiB  
Article
Circulating Cancer Associated Macrophage-like Cells as a Potential New Prognostic Marker in Pancreatic Ductal Adenocarcinoma
by Christine Nitschke, Benedikt Markmann, Leonie Konczalla, Jolanthe Kropidlowski, Thais Pereira-Veiga, Pasquale Scognamiglio, Martin Schönrock, Marianne Sinn, Marie Tölle, Jakob Izbicki, Klaus Pantel, Faik G. Uzunoglu and Harriet Wikman
Biomedicines 2022, 10(11), 2955; https://doi.org/10.3390/biomedicines10112955 - 17 Nov 2022
Cited by 5 | Viewed by 1694
Abstract
Background: Circulating Cancer Associated Macrophage-like cells (CAMLs) have been described as novel liquid biopsy analytes and unfavorable prognostic markers in some tumor entities, with scarce data for Pancreatic Ductal Adenocarcinomas (PDAC). Methods: Baseline and follow-up blood was drawn from resected curative (n [...] Read more.
Background: Circulating Cancer Associated Macrophage-like cells (CAMLs) have been described as novel liquid biopsy analytes and unfavorable prognostic markers in some tumor entities, with scarce data for Pancreatic Ductal Adenocarcinomas (PDAC). Methods: Baseline and follow-up blood was drawn from resected curative (n = 36) and palliative (n = 19) PDAC patients. A microfluidic size-based cell enrichment approach (ParsortixTM) was used for CAML detection, followed by immunofluorescence staining using pan-keratin, CD14, and CD45 antibodies to differentiate between CAMLs, circulating tumor cells (CTCs), and leukocytes. Results: CAMLs were detectable at baseline in 36.1% of resected patients and 47.4% of palliative PDAC patients. CAML detection was tumor stage independent. Follow-up data indicated that detection of CAMLs (in 45.5% of curative patients) was an independent prognostic factor for shorter recurrence-free survival (RFS) (HR: 4.3, p = 0.023). Furthermore, a combined analysis with CTCs showed the detectability of at least one of these cell populations in 68.2% of resected patients at follow-up. The combined detection of CAMLs and CTCs was also significantly associated with short RFS (HR: 8.7, p = 0.003). Conclusions: This pilot study shows that detection of CAMLs in PDAC patients can provide prognostic information, either alone or even more pronounced in combination with CTCs, which indicates the power of liquid biopsy marker analyses. Full article
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11 pages, 1819 KiB  
Article
Micronuclei in Circulating Tumor Associated Macrophages Predicts Progression in Advanced Colorectal Cancer
by Dimpal M. Kasabwala, Raymond C. Bergan, Kirby P. Gardner, Rena Lapidus, Susan Tsai, Mohammed Aldakkak and Daniel L. Adams
Biomedicines 2022, 10(11), 2898; https://doi.org/10.3390/biomedicines10112898 - 11 Nov 2022
Cited by 2 | Viewed by 1667
Abstract
Micronuclei (MN) are fragments of damaged nucleic acids which budded from a cell’s nuclei as a repair mechanism for chromosomal instabilities, which within circulating white blood cells (cWBCs) signifies increased cancer risk, and in tumor cells indicates aggressive subtypes. MN form overtime and [...] Read more.
Micronuclei (MN) are fragments of damaged nucleic acids which budded from a cell’s nuclei as a repair mechanism for chromosomal instabilities, which within circulating white blood cells (cWBCs) signifies increased cancer risk, and in tumor cells indicates aggressive subtypes. MN form overtime and with therapy induction, which requires sequential monitoring of rarer cell subpopulations. We evaluated the peripheral blood (7.5 mL) for MN in Circulating Stromal Cells (CStCs) in a prospective pilot study of advanced colorectal cancer patients (n = 25), identifying MN by DAPI+ structures (<3 µm) within the cellular cytoplasm. MN+ was compared to genotoxic induction, progression free survival (PFS) or overall survival (OS) hazard ratios (HR) over three years. MN were identified in 44% (n = 11/25) of CStCs, but were not associated with genotoxic therapies (p = 0.110) nor stage (p = 0.137). However, presence of MN in CStCs was independently prognostic for PFS (HR = 17.2, 95% CI 3.6–80.9, p = 0.001) and OS (HR = 70.3, 95% CI 6.6–752.8, p = 0.002), indicating a non-interventional mechanism in their formation. Additionally, MN formation did not appear associated with chemotherapy induction, but was correlated with tumor response. MN formation in colorectal cancer is an underlying biological mechanism that appears independent of chemotherapeutic genotoxins, changes during treatment, and predicts for poor clinical outcomes. Full article
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Review

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28 pages, 721 KiB  
Review
Circulating Biomarkers for Prediction of Immunotherapy Response in NSCLC
by Kah Yee Goh, Terence You De Cheng, Su Chin Tham and Darren Wan-Teck Lim
Biomedicines 2023, 11(2), 508; https://doi.org/10.3390/biomedicines11020508 - 9 Feb 2023
Cited by 6 | Viewed by 1919
Abstract
Non-small cell lung cancer (NSCLC) constitutes the majority of the lung cancer population and the prognosis is poor. In recent years, immunotherapy has become the standard of care for advanced NSCLC patients as numerous trials demonstrated that immune checkpoint inhibitors (ICI) are more [...] Read more.
Non-small cell lung cancer (NSCLC) constitutes the majority of the lung cancer population and the prognosis is poor. In recent years, immunotherapy has become the standard of care for advanced NSCLC patients as numerous trials demonstrated that immune checkpoint inhibitors (ICI) are more efficacious than conventional chemotherapy. However, only a minority of NSCLC patients benefit from this treatment. Therefore, there is an unmet need for biomarkers that could accurately predict response to immunotherapy. Liquid biopsy allows repeated sampling of blood-based biomarkers in a non-invasive manner for the dynamic monitoring of treatment response. In this review, we summarize the efforts and progress made in the identification of circulating biomarkers that predict immunotherapy benefit for NSCLC patients. We also discuss the challenges with future implementation of circulating biomarkers into clinical practice. Full article
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