Background: In oncogenic-driven non-small cell lung cancer (NSCLC), programmed death ligand 1 (PD-L1) expression is the result of a constitutive oncogenic activation leading to an immunosuppressive microenvironment. However, the relationship between the major driver mutations (KRAS, EGFR and ALK) and PD-L1 and other immune markers remains unclear. Gene expression signatures incorporating not only PD-L1 but also other components of the stroma might better capture the immune-context of these oncogenic subgroups. Method: A 7-gene 'immune signature' comprising CD4, CD8, PD-1, PD-L1, IFNG, GZMM and FOXP3 was included in a customized nCounter panel (NanoString Technologies), used in our clinical institution on a routine basis and designed to simultaneously screen for gene fusion drivers (ALK, ROS1, RET and NTRK1), MET overexpression and MET exon 14-skipping mutations in formalin-fixed paraffin embedded (FFPE) samples. A total of 296 advanced NSCLC patients from two different institutions were analyzed by the panel. Among them, 115 patients (38.9%) were also submitted to nextgeneration sequencing (NGS, Ion Torrent PGM® or GeneReader) . Analyses of variance (ANOVA) were used to describe statistical significance between immune response genes in the two major oncogenic groups: KRAS mutant (n¼33) andALK rearranged (n¼44), compared to wild-type (WT) tumor samples (n¼38). Result: Oncogenic genes (ALK, KRAS) were mutually exclusive. The analysis of the 7-gene signature revealed distinct expression patterns in the oncogenic biomarker groups. A significantly higher mRNA expression of CD4 and PD-L1 was found in ALK rearranged tumors compared to the KRAS mutant, and WT groups (p¼0.0014 and p¼0.0467, respectively). In addition, a trend was observed between GZMM mRNA levels and the oncogenic groups (p¼ 0.0665) whereas no association was found with the other immune genes (CD8, PD-1, IFNG, FOXP3). There was a significant linear correlation between CD4 and PD-L1 in ALK positive patients (p¼ 0.0214), but not in KRAS mutant samples (p¼ 0. 112). Unsupervised clustering across mRNA expression data from 296 samples using 7-immune-related genes showed two clusters, high expression for ALK-rearranged patients and low expression for KRAS mutant patients. The correlation between each of the immune genes was performed and a high correlation was found between PD-1 and FOXP3 (r¼0.9) and PD-1 with GZMM (r¼0.8). Conclusion: NSCLC tumors with ALK alterations show a distinct CD4 and PD-L1 immune profile when compared to KRAS and WT samples.Background: Atezolizumab is a humanized monoclonal antibody targeting PD-L1 that enhances tumour-specific T-lymphocyte responses. The efficacy and safety of atezolizumab versus docetaxel was demonstrated in patients with advanced NSCLC previously treated with chemotherapy in the phase III OAK trial (NCT02008227). Here, we report the cost-effectiveness in Canada of atezolizumab compared with docetaxel and nivolumab in previously-treated advanced NSCLC. Method: A cost-utility analysis was performed to estimate the cos...
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