The interplay between PD-L1 and vimentin in NSCLC patients: An exploratory analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20688-e20688
Author(s):  
Giuseppe Bronte ◽  
Maurizio Puccetti ◽  
Paola Cravero ◽  
Sara Ravaioli ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Survival Data ◽  
Immune Modulation ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Escape ◽  
Medical Systems ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Nsclc Patients

e20688 Background: The immune modulation is emerging as a key strategy in non-small cell lung cancer (NSCLC) patients management. PD-L1 has been the only biomarker validated for immunotherapy but it holds many limitations. Vimentin is one of the marker for epithelial-to-mesenchymal transition (EMT), a biological process which favors immune escape. We explored two issues: the correlation between PD-L1 and Vimentin expression in NSCLC samples and the prognostic value of PD-L1 and vimentin concordance in NSCLC patients. Methods: We collected all the NSCLC samples evaluable for both PD-L1 and Vimentin and recorded the relative available clinical and survival data, if written informed consent was present. PD-L1 and Vimentin were retrospectively assessed through immunohistochemistry (IHC) by using prediluted antibodies clones SP263 (Ventana Medical Systems, Tucson, AZ, USA) and anti Vimentin V9 (Ventana Medical Systems) on Benchmark XT Platform (Ventana Medical Systems). Biomarker expression was detected and semiquantitatively quantified as the percentage of immunopositive tumor cells on the total of tumor cells. We correlated PD-L1 and Vimentin expression through linear regression. We compared survival of patients with both PD-L1 and Vimentin 0% and all the others via Kaplan-Meier method by using MedCalc software version 18.11.3. Results: Ninety-nine samples underwent PD-L1 and Vimentin IHC analysis. A weak positive statistically significant correlation was found between the 2 biomarkers (r = 0.41; p < 0.001). For 40 patients survival data (from first NSCLC diagnosis) were available. Survival analysis showed that PD-L1 and Vimentin negative patients (n = 12) experienced not statistically significant longer survival (HR = 0.35; 95%CI: 0.08-1.51; p = 0.16). Conclusions: These preliminary findings suggest that an interplay can exist between PD-L1 and vimentin in NSCLC, but analysis in a wider population is necessary. Studies on the significance of this interplay for immunotherapy efficacy should be designed.

scholarly journals The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 823 ◽  
Author(s):  
Devis Pascut ◽  
Muhammad Yogi Pratama ◽  
Niem V.T. Vo ◽  
Rina Masadah ◽  
Claudio Tiribelli
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Immune Escape ◽  
Tumor Development ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Molecular Aspects

The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

scholarly journals ALDH3A1 Overexpression in Melanoma and Lung Tumors Drives Cancer Stem Cell Expansion, Impairing Immune Surveillance through Enhanced PD-L1 Output

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1963 ◽  
Author(s):  
Erika Terzuoli ◽  
Cristiana Bellan ◽  
Sara Aversa ◽  
Valerio Ciccone ◽  
Lucia Morbidelli ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Mononuclear Cells ◽  
Inflammatory Marker ◽  
Small Cell Lung Carcinoma ◽  
Peripheral Blood Mononuclear ◽  
Cell Lung Carcinoma ◽  
Mesenchymal Transition ◽  
Cox 2 ◽  
Nsclc Patients

Melanoma and non-small-cell lung carcinoma (NSCLC) cell lines are characterized by an intrinsic population of cancer stem-like cells (CSC), and high expression of detoxifying isozymes, the aldehyde dehydrogenases (ALDHs), regulating the redox state. In this study, using melanoma and NSCLC cells, we demonstrate that ALDH3A1 isozyme overexpression and activity is closely associated with a highly aggressive mesenchymal and immunosuppressive profile. The contribution of ALDH3A1 to the stemness and immunogenic status of melanoma and NSCLC cells was evaluated by their ability to grow in 3D forming tumorspheres, and by the expression of markers for stemness, epithelial to mesenchymal transition (EMT), and inflammation. Furthermore, in specimens from melanoma and NSCLC patients, we investigated the expression of ALDH3A1, PD-L1, and cyclooxygenase-2 (COX-2) by immunohistochemistry. We show that cells engineered to overexpress the ALDH3A1 enzyme enriched the CSCs population in melanoma and NSCLC cultures, changing their transcriptome. In fact, we found increased expression of EMT markers, such as vimentin, fibronectin, and Zeb1, and of pro-inflammatory and immunosuppressive mediators, such as NFkB, prostaglandin E2, and interleukin-6 and -13. ALDH3A1 overexpression enhanced PD-L1 output in tumor cells and resulted in reduced proliferation of peripheral blood mononuclear cells when co-cultured with tumor cells. Furthermore, in tumor specimens from melanoma and NSCLC patients, ALDH3A1 expression was invariably correlated with PD-L1 and the pro-inflammatory marker COX-2. These findings link ALDH3A1 expression to tumor stemness, EMT and PD-L1 expression, and suggest that aldehyde detoxification is a redox metabolic pathway that tunes the immunological output of tumors.

PHENOTYPIC HETEROGENEITY IN DISSEMINATED PROSTATE CANCER TUMOR CELLS: IMPLICATIONS IN EPITHELIAL TO MESENCHYMAL TRANSITION

2009 ◽  
Vol 181 (4S) ◽  
pp. 756-756
Author(s):  
Theodore D Koreckij ◽  
Todd M Morgan ◽  
Paul H Lange ◽  
Ilsa Coleman ◽  
Roger Coleman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Phenotypic Heterogeneity ◽  
Mesenchymal Transition ◽  
Cancer Tumor

scholarly journals Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5858
Author(s):  
Baris Kucukkaraduman ◽  
Ekin Gokce Cicek ◽  
Muhammad Waqas Akbar ◽  
Secil Demirkol Canli ◽  
Burcak Vural ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Epigallocatechin Gallate ◽  
Cancer Cell Lines ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Urolithin A

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

scholarly journals Evaluation of sensitivity and specificity of CanPatrol™ technology for detection of circulating tumor cells in patients with non-small cell lung cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingyao Li ◽  
Yi Liao ◽  
Yaling Ran ◽  
Guiyu Wang ◽  
Wei Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Survival Analysis ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Sensitivity And Specificity ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
Nsclc Patients

Abstract Background The early diagnosis of non-small cell lung cancer is of great significance to the prognosis of patients. However, traditional histopathology and imaging screening have certain limitations. Therefore, new diagnostical methods are urgently needed for the current clinical diagnosis. In this study we evaluated the sensitivity and specificity of CanPatrol™ technology for the detection of circulating tumor cells in patients with non-small cell lung cancer (NSCLC). Methods CTCs in the peripheral blood of 98 patients with NSCLC and 38 patients with benign pulmonary diseases were collected by the latest typing of CanPatrol™ detection technology. A 3-year follow-up was performed to observe their recurrence and metastasis. Kruskal-Wallis test was used to compare multiple groups of data, Mann-Whitney U test was used to compare data between the two groups, and ROC curve analysis was used to obtain the critical value. The COX risk regression and Kaplan-Meier survival analysis were performed in the 63 NSCLC patients who were effectively followed up. Results The epithelial, epithelial-mesenchymal, and total CTCs were significantly higher in NSCLC patients than that in patients with benign lung disease (P <  0.001). The mesenchymal CTCs of NSCLC patients was slightly higher than that of benign lung diseases (P = 0.013). The AUC of the ROC curve of the total CTCs was 0.837 (95% CI: 0.76-0.914), and the cut-off value corresponding to the most approximate index was 0.5 CTCs/5 ml, at which point the sensitivity was 81.6% and the specificity was 86.8%. COX regression analysis revealed that the clinical stage was correlated with patient survival (P = 0.006), while gender, age, and smoking were not (P > 0.05). After excluding the confounders of staging, surgery, and chemotherapy, Kaplan-Meier survival analysis showed that patients in stage IIIA with CTCs ≥0.5 had significantly lower DFS than those with CTCs < 0.5 (P = 0.022). Conclusions CTC positive can well predict the recurrence of NSCLC patients. CanPatrol™ technology has good sensitivity and specificity in detecting CTCs in peripheral blood of NSCLC patients and has a certain value for clinical prognosis evaluation.

scholarly journals Vimentin as a target for the treatment of COVID-19

2020 ◽  
Vol 7 (1) ◽  
pp. e000623
Author(s):  
Zhenlin Li ◽  
Denise Paulin ◽  
Patrick Lacolley ◽  
Dario Coletti ◽  
Onnik Agbulut
Keyword(s):  
Viral Infection ◽  
Lung Inflammation ◽  
Epithelial To Mesenchymal Transition ◽  
Attachment Site ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Cellular Target ◽  
Innovative Idea ◽  
Life Threatening ◽  
Approved Drugs

We and others propose vimentin as a possible cellular target for the treatment of COVID-19. This innovative idea is so recent that it requires further attention and debate. The significant role played by vimentin in virus-induced infection however is well established: (1) vimentin has been reported as a co-receptor and/or attachment site for SARS-CoV; (2) vimentin is involved in viral replication in cells; (3) vimentin plays a fundamental role in both the viral infection and the consequent explosive immune-inflammatory response and (4) a lower vimentin expression is associated with the inhibition of epithelial to mesenchymal transition and fibrosis. Moreover, the absence of vimentin in mice makes them resistant to lung injury. Since vimentin has a twofold role in the disease, not only being involved in the viral infection but also in the associated life-threatening lung inflammation, the use of vimentin-targeted drugs may offer a synergistic advantage as compared with other treatments not targeting vimentin. Consequently, we speculate here that drugs which decrease the expression of vimentin can be used for the treatment of patients with COVID-19 and advise that several Food and Drug Administration-approved drugs be immediately tested in clinical trials against SARS-CoV-2, thus broadening therapeutic options for this type of viral infection.

scholarly journals EMT Regulation by Autophagy: A New Perspective in Glioblastoma Biology

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 312 ◽  
Author(s):  
Barbara Colella ◽  
Fiorella Faienza ◽  
Sabrina Di Bartolomeo
Keyword(s):  
Transcription Factors ◽  
Tumor Cells ◽  
Tissue Repair ◽  
Epithelial To Mesenchymal Transition ◽  
Signalling Pathways ◽  
Migration And Invasion ◽  
Cell Resistance ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
New Perspective

Epithelial-to-mesenchymal transition (EMT) and its reverse process MET naturally occur during development and in tissue repair in vertebrates. EMT is also recognized as the crucial event by which cancer cells acquire an invasive phenotype through the activation of specific transcription factors and signalling pathways. Even though glial cells have a mesenchymal phenotype, an EMT-like process tends to exacerbate it during gliomagenesis and progression to more aggressive stages of the disease. Autophagy is an evolutionary conserved degradative process that cells use in order to maintain a proper homeostasis, and defects in autophagy have been associated to several pathologies including cancer. Besides modulating cell resistance or sensitivity to therapy, autophagy also affects the migration and invasion capabilities of tumor cells. Despite this evidence, few papers are present in literature about the involvement of autophagy in EMT-like processes in glioblastoma (GBM) so far. This review summarizes the current understanding of the interplay between autophagy and EMT in cancer, with special regard to GBM model. As the invasive behaviour is a hallmark of GBM aggressiveness, defining a new link between autophagy and EMT can open a novel scenario for targeting these processes in future therapeutical approaches.

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