Flow cytometry detection of cell type-specific expression of programmed death receptor ligand-1 (PD-L1) in colorectal cancer specimens

Saito, Akira; Tojo, Mineyuki; Kumagai, Yuko; Ohzawa, Hideyuki; Yamaguchi, Hironori; Miyato, Hideyo; Sadatomo, Ai; Naoi, Daishi; Ota, Gaku; Koinuma, Koji; Horie, Hisanaga; Lefor, Alan Kawarai; Sata, Naohiro; Kitayama, Joji

doi:10.1016/j.heliyon.2020.e05880

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…In this study, the percentage of EpCAM + CRC cells varied, but most samples (86.0%, 135/137) had more than 50% of these cells. In a study with 21 fresh CRC lesions that were analyzed using a protocol similar to ours, Satio et al (32) reported that both low and high counts of EpCAM + cells detected by flow cytometry in cell suspensions isolated from the lesions were tumor cells of a proportion of 64.0%±15.8% as compared to 72.1±20.0% observed in our study. This marginal difference might be attributed to the different compositions of the CRC cohorts analyzed.…”

Section: Discussionsupporting

confidence: 58%

Prognostic Significance of Immune Checkpoints HLA-G/ILT-2/4 and PD-L1 in Colorectal Cancer

Chen

Han

et al. 2021

Front. Immunol.

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Immune checkpoint inhibitors (ICIs) have become a promising area of research for cancer treatment. In addition to the well-known ICIs targeting PD-1/PD-L1, HLA-G/ILT-2/-4 is relatively new immune checkpoint that has been evaluated in early clinical trials in patients with advanced solid tumors. In this study, the expression of HLA-G (n=157), ILT-2/4 (n=82), and PD-L1 (n=70) in epithelial cell adhesion molecule (EpCAM)-positive colorectal cancer (CRC) cells was analyzed by multicolor flow cytometry, and the prognostic significance of these molecules was evaluated. In EpCAM+ CRC cells, the median percentages of HLA-G, ILT-2, ILT-4, and PD-L1 were 14.90%, 67.70%, 8.55% and 80.30%, respectively. In addition, a positive correlation was observed between them (all p<0.001). Higher levels of these immune checkpoint proteins are associated with lymph node metastasis. In addition to the AJCC stage (p=0.001), Kaplan-Meier survival analysis showed that higher levels of HLA-G (p=0.041), ILT-2 (p=0.060), ILT-4 (p<0.001), PD-L1 (p=0.012), HLA-GILT4 (p<0.001) and ILT-2ILT-4 (p<0.001) were significantly associated with shorter survival of CRC patients. When CRC patients were stratified by early and advanced AJCC stages, HLA-G levels were only related to the survival among CRC patients with early disease stage (p=0.024), while ILT-4 levels were significant for both CRC patients with early (p=0.001) and advanced (p=0.020) disease stages. Multivariate cox regression analysis revealed that advanced AJCC stage (HR=2.435; p=0.005) and higher ILT-4 levels (HR=2.198; p=0.063) were independent risk factors for poor outcomes in patients with CRC. In summary, among the immune checkpoints, HLA-G/ILT-2/4 and PD-L1, ILT-4 is the most significant prognostic indicator of CRC. This finding indicated that a combination of immunotherapy strategies, such as ILT-4 blockade, could improve the clinical outcomes in patients with cancer. Moreover, multicolor flow cytometry can be employed as a reliable and efficient, alternative to immunohistochemistry, for evaluating the immune checkpoint proteins expressed in tumor lesions.

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Section: Discussionsupporting

confidence: 58%

Prognostic Significance of Immune Checkpoints HLA-G/ILT-2/4 and PD-L1 in Colorectal Cancer

Chen

Han

et al. 2021

Front. Immunol.

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“…After that, cells were filtered with EASYstrainer 100 μm (Dutscher) to obtain a single-cell suspension. Last, CRCs were sorted by flow cytometry via identifying CD45( − )CD326( + )CD90( − ) to remove immune cells and stromal cells, according to the previous report ( 53 ). The tumor cells were expanded up to P1 for the in vitro and in vivo studies.…”

Section: Methodsmentioning

confidence: 99%

Mechanical manipulation of cancer cell tumorigenicity via heat shock protein signaling

Wong

Yin

et al. 2023

Sci. Adv.

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Biophysical cues of rigid tumor matrix play a critical role in cancer cell malignancy. We report that stiffly confined cancer cells exhibit robust growth of spheroids in the stiff hydrogel that exerts substantial confining stress on the cells. The stressed condition activated Hsp (heat shock protein)–signal transducer and activator of transcription 3 signaling via the transient receptor potential vanilloid 4–phosphatidylinositol 3-kinase/Akt axis, thereby up-regulating the expression of the stemness-related markers in cancer cells, whereas these signaling activities were suppressed in cancer cells cultured in softer hydrogels or stiff hydrogels with stress relief or Hsp70 knockdown/inhibition. This mechanopriming based on three-dimensional culture enhanced cancer cell tumorigenicity and metastasis in animal models upon transplantation, and pharmaceutically inhibiting Hsp70 improved the anticancer efficacy of chemotherapy. Mechanistically, our study reveals the crucial role of Hsp70 in regulating cancer cell malignancy under mechanically stressed conditions and its impacts on cancer prognosis–related molecular pathways for cancer treatments.

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“…Normal cells are surrounded the cancer cells in the body and these cells resemble each other, so it is challenging to diagnose and cure cancer. A few of the common procedures are used to diagnose cancers include Magnetic Resonance Imaging (MRI) [6,7], Computed Tomography (CT) [8][9][10], Positron Emission Tomography (PET) [9][10][11], flow cytometry [12,13], and biopsy [14][15][16][17][18][19][20]. Liquid biopsy, a non-invasive cancer cell detection method, calls for the collection of bodily fluids with little to no sample preparation [21].…”

Section: Introductionmentioning

confidence: 99%

Advanced electrocatalytic materials based biosensors for cancer cell detection – A review

et al. 2023

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Herein, we have highlighted the latest developments on biosensors for cancer cell detection. Electrochemical (EC) biosensors offer several advantages such as high sensitivity, selectivity, rapid analysis, portability, low‐cost, etc. Generally, biosensors could be classified into other basic categories such as immunosensors, aptasensors, cytosensors, electrochemiluminescence (ECL), and photo‐electrochemical (PEC) sensors. The significance of the EC biosensors is that they could detect several biomolecules in human body including cholesterol, glucose, lactate, uric acid, DNA, blood ketones, hemoglobin, and others. Recently, various EC biosensors have been developed by using electrocatalytic materials such as silver sulfide (Ag2S), black phosphene (BPene), hexagonal carbon nitrogen tube (HCNT), carbon dots (CDs)/cobalt oxy‐hydroxide (CoOOH), cuprous oxide (Cu2O), polymer dots (PDs), manganese oxide (MnO2), graphene derivatives, and gold nanoparticles (Au‐NPs). In some cases, these newly developed biosensors could be able to detect cancer cells with a limit of detection (LOD) of 1 cell/mL. In addition, many remaining challenges have to be addressed and validated by testing more real samples and confirm that these EC biosensors are more accurate and reliable to measure cancer cells in the blood and salivary samples.

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Flow cytometry detection of cell type-specific expression of programmed death receptor ligand-1 (PD-L1) in colorectal cancer specimens

Cited by 4 publications

References 40 publications

Prognostic Significance of Immune Checkpoints HLA-G/ILT-2/4 and PD-L1 in Colorectal Cancer

Prognostic Significance of Immune Checkpoints HLA-G/ILT-2/4 and PD-L1 in Colorectal Cancer

Mechanical manipulation of cancer cell tumorigenicity via heat shock protein signaling

Advanced electrocatalytic materials based biosensors for cancer cell detection – A review

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