Predictive Value of Alterations for Immune Checkpoint Inhibitors Treatment Outcomes in Patients With Cancer.

Lysine (K)-specific demethylase 5C () plays a significant role in the tumor cell proliferation, invasion, drug resistance and the regulation of tumor-related gene expression. Here, we aimed to investigate its predictive value in patients with cancers received immune checkpoint inhibitors (ICIs). We explored the predictive value of alterations and the association between alteration and immune landscape by using published cohort with clinical outcome and sequenced data from online database. The frequency of alterations was 2.1% across 48045 tumor samples with different cancers from 185 studies. alterations were correlated with markedly inferior overall survival (OS, 53 vs. 102 months, <0.0001) than those without. However, in ICI-treated group, patients with alterations had a substantially prolonged OS than the wild-type group (not reached vs. 18 months, =0.0041). The predictive value of alterations for ICI treatment outcome was not observed in patients with microsatellite-stable tumors (=0.2875). Intriguingly, patients with non-small-cell lung cancer and alterations receiving ICI had the better progression-free survival than wild type group (13.2 vs. 3.2 months, =0.0762). Mechanistically, altered tumors had dramatically higher TMB level and was associated with significantly higher level of CD8+ T cell infiltration and T effector signature. In conclusion, alterations was correlated with enhanced tumor immunogenicity and inflamed anti-tumor immunity, thus resulting in better treatment outcome in cancer patients receiving ICIs.