scholarly journals The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 540 ◽  
Author(s):  
Pei-Hung Chang ◽  
Min-Hsien Wu ◽  
Sen-Yu Liu ◽  
Hung-Ming Wang ◽  
Wen-Kuan Huang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Peripheral Lymphocytes ◽  
Blood Drawing ◽  
Programmed Cell Death 1

Circulating tumor cells (CTCs) and immune status are strongly related to cancer prognosis, although few studies have examined both factors. This prospective observational study (ClinicalTrials.gov: NCT02420600) evaluated whether CTCs, circulating cancer stem-like cells (cCSCs), and peripheral lymphocytes with/without Programmed cell death protein 1 (PD-1) expression were associated with prognosis among patients receiving palliative chemotherapy for initially unresectable, recurrent/metastatic head and neck squamous cell carcinoma (rmHNSCC). Thirty-four patients were enrolled between January 2015 and June 2016. Overall survival (OS) was associated with a higher CTC number (hazard ratio [HR]: 1.01, p = 0.0004) and cCSC ratio (HR: 29.903, p < 0.0001). Progression-free survival (PFS) was also associated with CTC number (HR: 1.013, p = 0.002) and cCSC ratio (HR: 10.92, p = 0.003). A CD8+ proportion of ≥ 17% was associated with improved OS (HR: 0.242, p = 0.004). A CD4: CD8 ratio of >1.2 was associated with poorer trend of PFS (HR: 2.12, p = 0.064). PD-1 expression was not associated with survival outcomes. Baseline CTCs, cCSC ratio, and CD8+ ratio may predict prognosis in rmHNSCC.

scholarly journals Characterization of programmed cell death-1 ligand (PD-L1) expression in circulating tumor cells (CTCs) of lung cancer

2016 ◽  
Vol 11 (2) ◽  
pp. S52 ◽  
Author(s):  
Rachel Krupa ◽  
David Lu ◽  
Ryon Graf ◽  
Jessica Louw ◽  
Lyndsey Dugan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Programmed Cell Death 1

scholarly journals Evaluation of PD-L1 Expression in Tumor Tissue of Patients with Lung Carcinoma and Correlation with Clinical and Demographic Data

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Gustavo Dix Junqueira Pinto ◽  
Luciano de Souza Viana ◽  
Cristovam Scapulatempo Neto ◽  
Sérgio Vicente Serrano
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Past History ◽  
Demographic Data ◽  
Immune Checkpoints ◽  
Programmed Cell Death 1 ◽  
History Of

Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1(programmed cell death 1)and its ligand PD-L1(programmed cell death 1 ligand 1)are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs). It was found that PD-L1 expression was more frequent in tumor cells than in IICs. Collective analysis by Tissue Microarray Assay (TMA) for PD-L1 expression in tumor cells and IICs did not reproduce the findings for separate individual analysis of tumor tissues. Patients with past history of smoking were more likely to express PD-L1 in tumor cells than those who never smoked. Patients with past history of smoking were less likely to have PD-L1 positive IICs compared to those who had never smoked. The immunohistochemical expression of PD-L1 in tumor cells and IICs did not correlate with survival.

scholarly journals PD-L1, an Important Immune Checkpoint Regulator, Is Suppressed by miR-34a in Head and Neck Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Kenjiro Higashi ◽  
Takenori Ogawa ◽  
Yuriko Saiki ◽  
Tomohiko Ishikawa ◽  
Yuta Kobayashi ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Cell Lines ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Expression Levels ◽  
Programmed Cell Death 1 ◽  
Hnscc Cell

Abstract Background: Key molecules regulating the immune checkpoint have shed light on the efforts to control several cancers. Recently, immune checkpoint inhibitors for cancer therapy such as antibodies against programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA4) have been developed. In head and neck squamous cell carcinomas (HNSCCs), such immune checkpoint inhibitors have come into clinical use and are expected to improve patients’ prognoses. Recently, miR-34a has been shown to be a downstream micro RNA of TP53 that regulates PD-L1 in several types of cancer. To reveal the correlations between miR-34a and PD-L1 in HNSCCs in terms of clinical significance, we analyzed 19 HNSCC cell lines.Methods: We measured the expression levels of miR-34a and PD-L1 in 10 HNSCC cell lines as well as in 9 of their derived acquired cisplatin (CDDP) resistant cell lines by qRT-PCR and Western blotting. Results were further analyzed by their TP53 statuses. We also investigated the changes in PD-L1 expression levels after miR-34a precursor- or inhibitor-mediated forced expression or suppression in HNSCC cell lines. Results: We observed inverse correlations between both mRNA and protein expression levels of miR-34a and PD-L1. No significant differences in miR-34a levels were observed with regard to TP53 status. Forced expression of miR-34a decreased PD-L1 expression, and suppression of miR-34a increased PD-L1 expression. Conclusion: Our present results suggest that miR-34a negatively regulates PD-L1 expression, possibly in a TP53 independent manner in HNSCC.

scholarly journals Cellulose Mediated Transferrin Nanocages for Enumeration of Circulating Tumor Cells for Head and Neck Cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Raj Shankar Hazra ◽  
Narendra Kale ◽  
Gourishankar Aland ◽  
Burhanuddin Qayyumi ◽  
Dipankar Mitra ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neck Cancer ◽  
Progression Free Survival ◽  
Capture Efficiency ◽  
Hydroxyl Groups ◽  
Cell Capture ◽  
Water Dispersible

Abstract Herein we report a hierarchically organized, water-dispersible ‘nanocage’ composed of cellulose nanocrystals (CNCs), which are magnetically powered by iron oxide (Fe3O4) nanoparticles (NPs) to capture circulating tumor cells (CTCs) in blood for head and neck cancer (HNC) patients. Capturing CTCs from peripheral blood is extremely challenging due to their low abundance and its account is clinically validated in progression-free survival of patients with HNC. Engaging multiple hydroxyl groups along the molecular backbone of CNC, we co-ordinated Fe3O4 NPs onto CNC scaffold, which was further modified by conjugation with a protein - transferrin (Tf) for targeted capture of CTCs. Owing to the presence of Fe3O4 nanoparticles, these nanocages were magnetic in nature, and CTCs could be captured under the influence of a magnetic field. Tf-CNC-based nanocages were evaluated using HNC patients’ blood sample and compared for the CTC capturing efficiency with clinically relevant Oncoviu platform. Conclusively, we observed that CNC-derived nanocages efficiently isolated CTCs from patient’s blood at 85% of cell capture efficiency to that of the standard platform. Capture efficiency was found to vary with the concentration of Tf and Fe3O4 nanoparticles immobilized onto the CNC scaffold. We envision that, Tf-CNC platform has immense connotation in ‘liquid biopsy’ for isolation and enumeration of CTCs for early detection of metastasis in cancer.

Prognostic value of programmed death-ligand 1 in solid tumors: A meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19121-e19121
Author(s):  
Jordan L Scott ◽  
Michelle Nadler ◽  
Alexandra Desnoyers ◽  
Fahad Almugbel ◽  
Rouhi Fazelzad ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Solid Tumors ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Stage Of Disease ◽  
Programmed Cell Death 1

e19121 Background: The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway plays a crucial role in cancer immuno-surveillance and is the target of approved immunotherapeutic drugs. Available data suggest a variable prognostic impact of PD-L1 expression in solid tumors. Methods: A systematic literature search of electronic databases identified publications exploring the effect of PD-L1 on overall survival (OS) and/or progression-free survival (PFS). Hazard ratios (HR) were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on disease site, stage of disease, and method of PD-L1 quantification using the Deeks method. Results: One hundred eighty-eight studies comprised of 212,748 patients met the inclusion criteria. PD-L1 expression was associated with worse OS (HR 1.32, 95% confidence interval (CI) 1.25 - 1.38; P < 0.001). There was significant heterogeneity between disease sites (subgroup P = 0.002) with pancreatic, hepatocellular and genitourinary cancers being associated with the highest magnitude of adverse outcome (Table). PD-L1 was also associated with worse overall PFS (HR 1.19, 95% CI 1.09 - 1.30; P < 0.001). Stage of disease did not significantly affect the results (subgroup P = 0.52), nor did the method of quantification (immunohistochemistry or mRNA) (subgroup P = 0.70). Conclusions: High expression of PD-L1 is associated with worse cancer outcomes albeit with significant heterogeneity between disease sites. The effect seems consistent in early stage and metastatic disease and is not sensitive to method of PD-L1 quantification. [Table: see text]

scholarly journals Harmonization of PD-L1 testing in oncology: a Canadian pathology perspective

2018 ◽  
Vol 25 (3) ◽  
pp. 209 ◽  
Author(s):  
D.N. Ionescu ◽  
M.R. Downes ◽  
A. Christofides ◽  
M.S. Tsao
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Head And Neck ◽  
Multiple Testing ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Future Directions ◽  
Appropriate Treatment ◽  
Programmed Cell Death 1 ◽  
Scoring Algorithms

Checkpoint inhibitors targeting the programmed cell death 1 protein (PD-1) and programmed cell death ligand 1 (PD-L1) are demonstrating promising efficacy and appear to be well tolerated in a number of tumour types. In non-small-cell lung cancer, head-and-neck squamous cell carcinoma, and urothelial carcinoma, outcomes appear particularly favourable in patients with high PD-L1 expression. However, assays for PD-L1 have been developed for individual agents, and they use different antibody clones, immunohistochemistry staining protocols, scoring algorithms, and cut-offs. Given that laboratories are unlikely to use multiple testing platforms, use of one PD-L1 assay in conjunction with a specific therapy will become impractical and could compromise treatment options. Methods to harmonize testing methods are therefore crucial to ensuring appropriate treatment selection. This paper focuses on lung, bladder, and head-and-neck cancer. It reviews and compares available PD-L1 testing methodologies, summarizes the literature about comparability studies to date, discusses future directions in personalized diagnostics, and provides a pathologist’s perspective on PD-L1 testing in the Canadian laboratory setting.

Isolation of Circulating Tumor Cells of Ovarian Cancer by Transferrin Immunolipid Magnetic Spheres and Its Preliminary Clinical Application

Nano LIFE ◽  
2019 ◽  
Vol 09 (01n02) ◽  
pp. 1940001 ◽  
Author(s):  
Li Zuo ◽  
Wei Niu ◽  
Anqi Li
Keyword(s):  
Ovarian Cancer ◽  
Survival Rate ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Progression Free Survival ◽  
Cancer Prognosis ◽  
Free Survival ◽  
Magnetic Spheres ◽  
Positive Rate

Circulating tumor cells (CTCs) play an important role in cancer prognosis, treatment monitoring and metastasis diagnosis. However, due to the extremely low concentration of CTC in the peripheral blood, its isolation and enrichment are critical steps for early diagnosis. Herein, we used the transferrin modified lipid magnetic spheres for the isolation of ovarian cancer CTCs, and studied the relationship between the CTCs count and the clinical case parameters, prognosis of ovarian cancer. The result showed that no CTC was found in the peripheral blood of 30 patients with benign cysts, and 34 out of 46 patients with ovarian cancer were positive for CTC, with a positive rate of 73.9%. Analysis of the parameters of the clinical cases showed that the positive rate of CTC was related to the clinical stages, and that it was not significantly related to the age, histopathological types and pathological grades of patients. Of the 34 CTC-positive patients, 18 had progression-free survival, with a survival rate of 52.9%, and of the 11 CTC-negative patients, 9 had progression-free survival, with a survival rate of 81.8%. The results showed that the transferrin lipid magnetic spheres prepared in this study, could effectively isolate the CTCs in the peripheral blood of patients with ovarian cancer, that the level of CTC in ovarian cancer patients was related to its clinical stage, and that the progression-free survival of the patients with a high level of CTCs was relatively short. Therefore, this study shows that the transferrin lipid magnetic sphere can achieve effective isolation of ovarian cancer CTC, which can be used as an auxiliary diagnostic method in comprehensive diagnosis of ovarian cancer.

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