The approval of monoclonal antibodies against programmed death-ligand 1 (PD-L1) and programmed cell death protein (PD1), has changed the landscape of cancer treatment. To date, many Immune Checkpoint Inhibitors (ICIs) have been approved by the FDA for the treatment of metastatic cancer as well as locally recurrent advanced cancer. However, immune-related adverse events (irAEs) of ICIs highlight the need for biomarker analysis with strong predictive value. Liquid biopsy is an important tool for clinical oncologists to monitor cancer patients and administer or change appropriate therapy. CTCs frequently express PD-L1 and this constitutes a clinically useful and non-invasive method to assess PD-L1 status in real time. This review summarizes all the latest findings about the clinical significance of CTC for the management of cancer patients during administration of immunotherapy and mainly focuses on the assessment of PD-L1 expression in CTCs.

In a power plant that uses seawater as a coolant, a debris filter is required to remove foreign substances from the seawater, and differential pressure leads to a decrease in the coolant flow rate, leading to a decrease in power generation efficiency. In this study, analysis was performed under different initial flow velocity conditions of 1.5m/s, 2.0m/s, and 2.5m/s for a debris filter used in a power plant to understand flow characteristics in CTCS. The flow and differential pressure characteristics of a CTCS with an installed debris filter were considered in a comparative analysis of velocity, pressure, and turbulent kinetic energy distribution. The results confirmed that a vortex was generated in the pipe with the debris filter, apparently due to the collision of the flow with the bracket of the debris filter. As the flow rate increased, the range of the vortex increased, causing a loss in flow.

Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood. This study aims at understanding the molecular features within CTCs in relation to their metastatic potential. Using in vitro CTC models, in which breast cancer cell lines are cultured in non-adherent conditions simulating the microenvironment in the blood stream, we found that suspension culture resulted in resistance to TNF-related apoptosis inducing ligand (TRAIL)-mediated cell death. Such a resistance was directly correlated with a reduction in surface and total levels of DR5 protein. In the non-adherent state, cells underwent rapid autophagic flux characterized by an accumulation of autophagosome organelles. Notably, DR5 was translocated to autophagosomes and underwent lysosomal degradation. Our data suggest that CTCs may evade TNF cytokine mediated immune surveillance through downregulation of DR expression. The data warrants further studies in cancer patients to find the status of DRs and other molecular features within primary CTCs in relation to disease progression or chemoresistance.

Enzalutamide is a second-generation androgen-receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker after enzalutamide administration. A retrospective subgroup analysis and prognostic survey of 43 patients with mCRPC and bone metastases, treated in Juntendo University-affiliated hospitals from 2015–2022, were conducted. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months post-treatment. Relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with CTCs at baseline. Furthermore, patients showing negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positive continuation. Two biomarkers–higher hemoglobin at baseline and achieving negative-reversion of CTCs–were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in treatment of mCRPC.

Separation and interpretation of rebellious Circulating Tumor Cells (CTCs) originating from the primary tumor or cancer tissue plays a significant role in diagnostics, cancer progression analyses, suitable medicine exploration, and treatment proficiency examination. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, leading to new tumors in that area. Although a dramatic rate of deaths begins from spreading CTCs around the body, valuable measures have been made to control their development. However, the first step is separating these harmful cells from the bloodstream and investigating their features. Having examined the characteristics of CTCs as cancer’s main strength, researchers can introduce complementary treatments that can affect cancerous cells without damaging the healthy cells. Therefore, according to their unique characteristics, numerous techniques have been established for continuous and fast separation and sorting of CTCs. Nevertheless, few separators enjoy the efficient performance and appropriate accuracy and can be produced in mass numbers due to the available fabrication equipment. Microfabrication advancements enable separators to combine the advantages of active and passive methods in a small-scale platform for probing individual cells and separation purposes. Reduction in reagents, sample volume, analysis time, and less harmfulness to patients are some of the motivations that encourage researchers to employ microfluidic instruments for CTCs separation from other blood cells over the last two decades. However, microfabrication limitations mean effective separators, and the diagnostic option they provide, are not readily available. Addressing these limitations requires optimizing the design and fabrication of separators such that they are reduced in their size and fabrication cost, while also maintaining high-throughput separating capability. The emergence of the Lab-On-a-Chip (LOC) and then Lab-On-a-CD (LOCD) technologies, having more inherent benefits than conventional microfluidic devices, has created new opportunities and become increasingly widespread in recent years. Evidence suggests that employing single methodologies or integrating approaches without sufficient understanding of potential outcomes is unlikely to result in successful diagnostic results. This paper contributes an extensive review of several separation systems, including fundamental theories and experimental details, and describes detailed operating principles and device performance.