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 ◽  
...  
2021 ◽  
Vol 2 (3) ◽  
pp. 31-41
Author(s):  
D. A. Kharagezov ◽  
Yu. N. Lazutin ◽  
E. Yu. Zlatnik ◽  
A. B. Sagakyants ◽  
E. A. Mirzoyan ◽  
...  

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.


2021 ◽  
Author(s):  
Yanhua Li ◽  
Kun Tang ◽  
Xia Zhang ◽  
Wei Pan ◽  
Na Li ◽  
...  

Cancer immunotherapy has remarkably improved the therapeutic effect of melanoma and non-small cell lung cancer in the clinic. Nevertheless, it showed disappointing clinical outcomes for treating immunosuppressive tumors, wherein the...


2020 ◽  
Author(s):  
Jiesheng Li ◽  
Zemin Zhang ◽  
Xianwen Ren

ABSTRACTSingle cell RNA-seq has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T cell differentiation and activation, here we proposed a computational method named as IDEA to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq dataset of 12,346 T cells from non-small cell lung cancer. We found most genes tend to dominantly express one isoform in single T cells, enabling typing T cells according to the isotypes given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8+ T cells and 456 genes in CD4+ T cells. Functional annotation suggests that the preferred isoforms involved in coding/non-coding switches, transcription start site changes, gains/losses of domains and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new lights into the regulatory mechanisms of tumor-infiltrating T cells.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Ashish Gupta ◽  
Aung Tun ◽  
Katy Ticona ◽  
Aam Baqui ◽  
Elizabeth Guevara

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.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Adam Antczak ◽  
Dorota Pastuszak-Lewandoska ◽  
Paweł Górski ◽  
Daria Domańska ◽  
Monika Migdalska-Sęk ◽  
...  

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.


Immunity ◽  
2021 ◽  
Vol 54 (3) ◽  
pp. 586-602.e8
Author(s):  
Shin-Heng Chiou ◽  
Diane Tseng ◽  
Alexandre Reuben ◽  
Vamsee Mallajosyula ◽  
Irene S. Molina ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3116
Author(s):  
Mohamed Eltahir ◽  
Johan Isaksson ◽  
Johanna Sofia Margareta Mattsson ◽  
Klas Kärre ◽  
Johan Botling ◽  
...  

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.


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