RAD51B(me) Levels as a Potential Predictive Biomarker for PD-1 Blockade Response in Non-Small Cell Lung Cancer

Lung cancer (LC) cells frequently express high levels of programmed death-ligand 1 (PD-L1). Although these levels grossly correlate with the likelihood of response to specific checkpoint inhibitors, the response prediction is rather imperfect, and more accurate predictive biomarkers are mandatory. We examined the methylation profile of RAD51B (RAD51B(me)) as a candidate predictive biomarker for anti-PD-1 therapy efficacy in non-small cell lung cancer (NSCLC), correlating with patients’ outcome. PD-L1 immunoexpression and RAD51B(me) levels were analysed in NSCLC samples obtained from patients not treated with anti-PD-1 (Untreated Cohort (#1)) and patients treated with PD-1 blockade (Treated Cohort (#2)). Of a total of 127 patients assessed, 58.3% depicted PD-L1 positivity (PD-L1(+)). RAD51B(me) levels were significantly associated with PD-L1 immunoexpression. Patients with PD-1 blockade clinical benefit disclosed higher RAD51B(me) levels (p = 0.0390) and significantly lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025). Combining RAD51B(me+) with PD-L1(+) improved the sensitivity of the test to predict immunotherapy response. PD-L1(+) was also associated with lower risk of death (HR 0.35; 95% CI: 0.15–0.81; p = 0.014). Thus, RAD51B(me) levels might be combined with validated predictive biomarker PD-L1 immunostaining to select patients who will most likely experience clinical benefit from PD-1 blockade. The predictive value of RAD51B(me) should be confirmed in prospective studies.