The DIREct-On (Durable Immunotherapy Response Estimation by immune profiling and ctDNA) model incorporates three non-invasive biomarkers, pre-treatment ctDNA-normalized bTMB, circulating CD8 T cell fraction and on-treatment early ctDNA dynamics, and it was initially constructed to predict the clinical response of NSCLC patients who received anti-PD-(L)1 immunotherapy (97). This evidence concerns the gene CD8A and non-small cell lung carcinoma.