Immune checkpoint inhibitors (ICIs) are currently one of the most promising therapy options in the field of oncology. Although the first pivotal ICI trial results were published in 2011, few biomarkers exist to predict their therapy outcome. PD-L1 expression and tumor mutational burden (TMB) were proven to be sometimes-unre‑ liable biomarkers. | Wessolly et al. BMC Cancer 2022 22 46 https s12885-021-09111-w RESEARCH Open Access Digital gene expression analysis of NSCLC-patients reveals strong immune pressure resulting in an immune escape under immunotherapy Michael Wessolly1 2 Susann Stephan Falkenau3 Anna Streubel3 Marcel Wiesweg4 Sabrina Borchert1 2 Elena Mairinger1 Jens Kollmeier5 Henning Reis1 6 Torsten Bauer5 Kurt Werner Schmid1 Thomas Mairinger3 Martin Schuler2 4 and Fabian D. Mairinger1 2 Abstract Background Immune checkpoint inhibitors ICIs are currently one of the most promising therapy options in the field of oncology. Although the first pivotal ICI trial results were published in 2011 few biomarkers exist to predict their therapy outcome. PD-L1 expression and tumor mutational burden TMB were proven to be sometimes-unre liable biomarkers. We have previously suggested the analysis of processing escapes a qualitative measurement of epitope structure alterations under immune system pressure to provide predictive information on ICI response. Here we sought to further validate this approach and characterize interactions with different forms of immune pressure. Methods We identified a cohort consisting of 48 patients with advanced non-small cell lung cancer NSCLC treated with nivolumab as ICI monotherapy. Tumor samples were subjected to targeted amplicon-based sequencing using a NetChop and MHC binding verified by NetMHC. The NanoString nCounter platform was utilized to provide gene panel of 22 cancer-associated genes covering 98 mutational hotspots. Altered antigen processing was predicted by expression data of 770 immune-related genes. Patient data from 408 patients with NSCLC were retrieved from The Cancer Genome Atlas TCGA as a validation cohort. Results The two immune escape mechanisms of PD-L1 expression TPS score n 18 and presence of altered anti gen processing n 10 are mutually non-exclusive and can occur in the same patient n 6 . Both mechanisms have exclusive influence on .
