Pre-existing TCR clones drive major pathological responses in HNSCC patients treated with dual immune checkpoint inhibitors - PubMed
4 hours ago
- #TCR clones
- #immune checkpoint inhibitors
- #HNSCC
- Pre-existing TCR clones dominate post-treatment CD8 T-cell pools in HNSCC patients treated with dual immune checkpoint inhibitors (ICI), regardless of clinical outcome.
- Major pathological responses (MPR) are characterized by higher abundance and greater expansion of 'super-expanded' TCR clones.
- The TCR Adaptivity Index (TAI) was developed to quantify coordinate flux of TCR clones and emerged as the most significant parameter associated with MPR.
- Clonal expansion in non-MPR cases was uncoupled from productive, therapy-induced transcriptional reprogramming observed in MPR.
- Expansion dynamics positively correlated with predicted tumor reactivity as calculated by the Tumor Reactive Signature (TRS) score.
- A TRS-integrated TAI remained significantly correlated with MPR, providing a framework to predict therapeutic efficacy.