What is the significance of TP53 and KRAS mutation for immunotherapy in non-small cell lung cancer?

Increasing evidences including PD-L1 expression (1,2), tumor mutation burden (TMB) (3,4), and the intensity of CD8+ T cell infiltrates (5-7) have been respectively certified as predictive biomarkers of response to immunotherapy. More recently, our study identified TP53/KRAS mutation may be another applicable factor to predict response to PD-1 blockade in non-small cell lung cancer (NSCLC) (8). This result has aroused some discussions. Dr. Tawee Tanvetyanon (9) raises a question of when is KRAS or TP53 mutation predictive of response to immunotherapy for lung cancer? He points out that it is not adequate enough to demonstrate the predictive value of KRAS mutation independently from TMB and that TP53 or KRAS mutation may be served as a predictive biomarker along with high TMB.