TP53 and LRP1B Co-Wild Predicts Improved Survival for Patients with LUSC Receiving Anti-PD-L1 Immunotherapy.

Immunotherapy brought long-term benefits for partial patients with lung squamous cell carcinoma (LUSC). The predictor of anti-PD-L1 therapy was controversial and limited in LUSC. We aimed to explore novel biomarker for LUSC immunotherapy and the potential mechanism. Five hundred and twenty-five Chinese patients (Geneplus cohort) with LUSC underwent targeted sequencing and were involved to explore the genomic profiling. and were the most frequently recurrent genes and correlated to higher tumor mutational burden (TMB). We observed that LUSC patients with and co-wild (co-wild type) were associated with better survival of anti-PD-L1 therapy compared with mutant or mutant (mutant type) in POPAR/OAK cohort. Copy-number variation (CNV) and whole genome doubling (WGD) data from TCGA LUSC cohort were obtained to assess the CNV events. There were fewer CNV alterations and lower chromosome instability in patients with / co-wild compared with those with / mutant. RNA expression data from the TCGA LUSC cohort were collected to explore the differences in RNA expression and tumor immune microenvironment (TIME) between mutant and co-wild groups. The / co-wild type had a significantly increased proportion of multiple tumor-infiltrating lymphocytes (TILs), including activated CD8 T cell, activated dendritic cell (DC), and effector memory CD8 T cell. Immune-related gene sets including checkpoint, chemokine, immunostimulatory, MHC and receptors were enriched in the co-wild type. In conclusion, / co-wild LUSC conferred an elevated response rate in anti-PD-L1 therapy and improved survival, which was associated with a chromosome-stable phenotype and an activated immune microenvironment.