Tissue and peripheral T cell receptor repertoire predicts immunotherapy response and progression-free survival in NSCLC patients

Immunotherapy has opened new avenues of treatment for patients with advanced non-small cell lung cancer (NSCLC) without previous hope of survival. Unfortunately, only a small percentage of patients benefit from it and there is not an effective biomarker to predict patients' response. Since T cells are key effectors of antitumor immunity, T cell receptor (TCR) has emerged as a potential predictive biomarker. Here, we evaluated the potential of baseline TCR repertoire, as a predictive biomarker in advanced NSCLC patients treated with pembrolizumab at first-line. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCRβ/γ was performed. We found an uneven tumor-infiltrating TCRβ repertoire, and the use of various tumor-infiltrating and circulating TRBV/J genes were able of predicting the immunotherapy response. Our results support the potential of evaluating tissue and circulating TCRβ repertoire prior to pembrolizumab, revealing it as a promising immunotherapy response biomarker in NSCLC patients.