Circulating CD137+T cells as an immune biomarker for response to anti-PD1 immunotherapy in NSCLC patients

Anti-PD1 treatment, administered alone (PDL1>50%) or in combination with chemotherapy (PDL1<50%), is the standard of care in the first-line setting in non-oncogenic addicted Non-Small Cell Lung Cancer (NSCLC). Despite the success of these treatments, only 20-30% of these patients fully respond to these therapies, highlighting the need to identify novel biomarkers to optimize treatment strategies. CD137+ T cells are identified as activated and tumor-specific T cells. In several solid tumors, their levels correlate with responses to anti-PD1 therapy. In this study, we evaluate the levels of CD137+ T cells in NSCLC patients as biomarker of response to immunotherapy. PBMCs derived from 82 NSCLC patients undergoing both first- (from 2020-today) and second-line (from 2016 to 2019) anti-PD1 treatment were analyzed at baseline by cytofluorimetry for the expression of CD3, CD4, CD8, CD137, and PD1 molecules. These parameters were correlated with clinical outcomes. Results show that in all patients, the levels of circulating CD137+T cells are significantly higher in responder patients (Rs) than in non-responders (NRs) (p=0.02), and that these high levels were ascribed to both CD8 (p=0.02) and CD4 (p=0.03) T cell populations. Moreover, patients with a percentage of CD3+CD137+>1.26% had prolonged OS (p=0.007) and PFS (p=0.002). Rs also showed high levels of CD137+PD1+T cells compared with NR (p=0.002) ascribed to both CD8 and CD4 T cells (p=0.02 and p=0.03, respectively). Patients undergoing first- and second-line treatment were further analyzed and compared. The group of patients receiving first-line therapy had higher levels of CD137+ (p=0.005) and CD137+PD1+ (p<0.001) T cells compared with the other group, suggesting that naïve patients had a more activated immune system. Our results indicate that levels of circulating CD137+ T cells could predict the response to anti-PD1 therapy in NSCLC patients and could be used as biomarker for the success of anticancer treatmen