Tissue and Peripheral T-cell Repertoire Predicts Immunotherapy Response and Progression-Free Survival in NSCLC Patients

Abstract

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 it is still not well understood which tumor characteristics can be used to predict immunotherapy response. As the key cellular effectors of antitumor immunity, T cells are endowed with specialized T cell receptors (TCRs) to recognize and eliminate cancer cells. Here, we evaluated the potential of TCR repertoire as a predictive biomarker in patients treated with immunotherapy. With this aim, advanced NSCLC patients treated with immunotherapy at first-line were included. After obtaining peripheral blood and tissue samples at baseline, next-generation sequencing targeting TCRβ/γ was performed. Beyond TCR metrics, clonal space of the most frequent clones was determined. We found a positive association between uneven tumor-infiltrating TCRβ repertoire and the immunotherapy response. Moreover, the use of various tumor-infiltrating and circulating TRBV/J genes predicted the immunotherapy response. Our results indicate the importance of evaluating tissue and circulating TCRβ repertoire prior immunotherapy, showing it as a promising immunotherapy response biomarker in NSCLC patients.