scholarly journals CTLA-4 Expression and Polymorphisms in Lung Tissue of Patients with Diagnosed Non-Small-Cell Lung Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Adam Antczak ◽  
Dorota Pastuszak-Lewandoska ◽  
Paweł Górski ◽  
Daria Domańska ◽  
Monika Migdalska-Sęk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Lung Cancer ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Small Cell ◽  
Cancer Tissue ◽  
Small Cell Lung

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is a potent immunoregulatory molecule that downregulates T-cell activation and thus influences the antitumor immune response. CTLA-4 polymorphisms are associated with various cancers, and CTLA-4 mRNA/protein increased expression is found in several tumor types. However, most of the studies are based on peripheral blood mononuclear cells, and much less is known about the relationship between CTLA-4 expression, especially gene expression, and its polymorphic variants in cancer tissue. In our study we assessed the distribution of CTLA-4 two polymorphisms (+49A/G and −318C/T), using TaqMan probes (rs231775 and rs5742909, resp.), andCTLA-4gene expression in real-time PCR assay in non-small-cell lung cancer (NSCLC) tissue samples. The increasedCTLA-4expression was observed in the majority of NSCLC patients, and it was significantly correlated with TT genotype (−318C/T) and with tumor size (T2 versus T3 + T4). The presence of G allele and GG genotype in cancer tissue (+49A/G) was significantly associated with the increased NSCLC risk. Additionally, we compared genotype distributions in the corresponding tumor and blood samples and found statistically significant differences. The shift from one genotype in the blood to another in the tumor may confirm the complexity of gene functionality in cancer tissue.

scholarly journals Biomarkers for non-small cell lung cancer immunotherapy

2021 ◽  
Vol 2 (3) ◽  
pp. 31-41
Author(s):  
D. A. Kharagezov ◽  
Yu. N. Lazutin ◽  
E. Yu. Zlatnik ◽  
A. B. Sagakyants ◽  
E. A. Mirzoyan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung

The discovery of immune checkpoint inhibition has revolutionized the treatment of many solid malignancies, including non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors (ICI) can restore the antitumor immune response by blocking the inhibition of T-cell activation. Anti-programmed death-ligand 1 (PD-L1) is currently the main biomarker of the effectiveness of anti-PD-1 / PD-L1 blockade in the treatment of NSCLC without driver mutations. High tumor mutational burden suggests an increased neoantigens load and has been associated with the effectiveness of ICI therapy. Microsatellite instability, a biomarker approved for immunotherapy across solid tumors, but it is uncommon in NSCLC. Primary resistance to ICIsis characteristic of NSCLC with driver mutations, acquired is associated with immunoediting resulting in the depletion of potentially immunogenic neoantigens. The review discusses recent advances and future directions for predicting the results of immunotherapy in patients with NSCLC.

Clinical value of measuring T-cell activation and proliferation using multiplexed quantitative fluorescence in non-small cell lung cancer (NSCLC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 11610-11610 ◽  
Author(s):  
Kurt Alex Schalper ◽  
Nikita Mani ◽  
Maria Toki ◽  
Daniel E. Carvajal-Hausdorf ◽  
Roy S. Herbst ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Lung Cancer ◽  
Cell Activation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Value ◽  
Quantitative Fluorescence

scholarly journals Invasive Aspergillosis in a Patient with Stage III (or 3a or 3b) Non-Small-Cell Lung Cancer Treated with Durvalumab

2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Ashish Gupta ◽  
Aung Tun ◽  
Katy Ticona ◽  
Aam Baqui ◽  
Elizabeth Guevara
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Lung Cancer ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Left Lung ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung

Durvalumab is a therapeutic monoclonal antibody that blocks the checkpoint inhibitor, programmed death ligand 1 (PD-L1), resulting in T-cell activation and an antitumor response. Durvalumab is approved for patients with unresectable stage III non-small-cell lung cancer (NSCLC) which has not progressed following platinum-based chemoradiotherapy. A 63-year-old man presented to the emergency department with a 15-day history of increasing shortness of breath. Several months previously, he had been diagnosed with a poorly differentiated stage IIIB NSCLC. He had completed six cycles of chemotherapy with paclitaxel and carboplatin and four cycles of immunotherapy with durvalumab 13 days before his emergency hospital admission. Computed tomography (CT) imaging showed a large left-sided loculated hydropneumothorax suggestive of empyema, patchy opacification of the left lung, and a left upper lobe lung mass. Histology of the cell block from the pleural fluid and decorticated lung tissue showed hyphae suggestive of invasive Aspergillus fumigatus. Treatment with voriconazole resulted in clinical improvement. To our knowledge, this is the first reported case of pleural aspergillosis in a patient treated with durvalumab. However, the increasing use of immune checkpoint inhibitors in oncology requires increased awareness by clinicians of immune-related adverse events (irAEs) due to opportunistic infection.

scholarly journals Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3116
Author(s):  
Mohamed Eltahir ◽  
Johan Isaksson ◽  
Johanna Sofia Margareta Mattsson ◽  
Klas Kärre ◽  
Johan Botling ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cluster Analysis ◽  
Small Cell Lung Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Response Prediction ◽  
Small Cell ◽  
Small Cell Lung ◽  
Activation Markers ◽  
Protein Levels

Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select patients for immunotherapy, but its predictive accuracy is modest. The aim of our study was to evaluate a proteomic assay for the analysis of patient plasma in the context of immunotherapy. Pretreatment plasma samples from 43 NSCLC patients who received anti-PD-(L)1 therapy were analyzed using a proximity extension assay (PEA) to quantify 92 different immune oncology-related proteins. The plasma protein levels were associated with clinical and histopathological parameters, as well as therapy response and survival. Unsupervised hierarchical cluster analysis revealed two patient groups with distinct protein profiles associated with high and low immune protein levels, designated as “hot” and “cold”. Further supervised cluster analysis based on T-cell activation markers showed that higher levels of T-cell activation markers were associated with longer progression-free survival (PFS) (p < 0.01). The analysis of single proteins revealed that high plasma levels of CXCL9 and CXCL10 and low ADA levels were associated with better response and prolonged PFS (p < 0.05). Moreover, in an explorative response prediction model, the combination of protein markers (CXCL9, CXCL10, IL-15, CASP8, and ADA) resulted in higher accuracy in predicting response than tumor PD-L1 expression or each protein assayed individually. Our findings demonstrate a proof of concept for the use of multiplex plasma protein levels as a tool for anti-PD-(L)1 response prediction in NSCLC. Additionally, we identified protein signatures that could predict the response to anti-PD-(L)1 therapy.

p53-regulated GML gene expression in non-small cell lung cancer: Relation to cisplatin chemosensitivity

Lung Cancer ◽  
2000 ◽  
Vol 29 (1) ◽  
pp. 193
Author(s):  
M Higashiyama ◽  
K Kodama ◽  
H Yokouchi ◽  
K Takami ◽  
Y Miyoshi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

Effects of fine air particulates on gene expression in non-small-cell lung cancer

2017 ◽  
Vol 62 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Biao Yang ◽  
Xinming Li ◽  
Dongmei Chen ◽  
Chunling Xiao
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Cell-autonomous immune gene expression is repressed in pulmonary neuroendocrine cells and small cell lung cancer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Ling Cai ◽  
Hongyu Liu ◽  
Fang Huang ◽  
Junya Fujimoto ◽  
Luc Girard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Neuroendocrine Cells ◽  
Immune Gene ◽  
Small Cell Lung ◽  
Immune Gene Expression ◽  
Pulmonary Neuroendocrine Cells

AbstractSmall cell lung cancer (SCLC) is classified as a high-grade neuroendocrine (NE) tumor, but a subset of SCLC has been termed “variant” due to the loss of NE characteristics. In this study, we computed NE scores for patient-derived SCLC cell lines and xenografts, as well as human tumors. We aligned NE properties with transcription factor-defined molecular subtypes. Then we investigated the different immune phenotypes associated with high and low NE scores. We found repression of immune response genes as a shared feature between classic SCLC and pulmonary neuroendocrine cells of the healthy lung. With loss of NE fate, variant SCLC tumors regain cell-autonomous immune gene expression and exhibit higher tumor-immune interactions. Pan-cancer analysis revealed this NE lineage-specific immune phenotype in other cancers. Additionally, we observed MHC I re-expression in SCLC upon development of chemoresistance. These findings may help guide the design of treatment regimens in SCLC.

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