Molecular profiling in HNSCC patients targets potential responsiveness to ICIs

Abstract

Immunotherapy is emerging as a valid therapeutic strategy for various cancers although only a subset of patients responding to the therapy. The response to immunotherapy remains low for many cancer types because of poor ability to appropriately classify responding patients. We analyzed TCGA cohort of HNSCC patients in relation to a 26 immune gene set and cell types to define signaling pathways associated with resistance to immune checkpoint blockade. Results were validated on a cohort of 102 HNSCC patients under treatment with PD-L1 inhibitors and by in vitro experiments. Using bioinformatic approach, we observed a significant association between the gene set and TP53 gene status and other predictors of ICIs response in HNSCC patients. The presence of both TP53 mutation and co-mutations was associated with significantly higher levels of the immune gene expression than in lesions with only the TP53 mutated. We also observed that higher level of a MYC signature was associated with lower level of the immune gene expression. In vitro and cohort validation corroborated the evidence. SIGNIFICANCEImmune gene signature sets represent biomarkers to be implemented for the better classification of those HNSCC patients responsive to immunotherapy. A particular advantage of these biomarkers is the ability to characterize HNSCC patients using tumor tissues easily applicable in clinical setting.