頭頸部癌におけるPD-1阻害剤治療成績予測のための血漿ctDNAおよび末梢T細胞受容体レパトワの初期キネティクス調査
Enrique Sanz-Garcia1, Shirin Soleimani2, Jeff P Bruce1
1Princess Margaret Cancer Centre Toronto, Ontario Canada.
Purpose:
Immune checkpoint blockade (ICB) therapies targeting the PD-1 axis have significantly improved survival in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Circulating tumor DNA (ctDNA) and peripheral T cell receptor (TCR) repertoires are emerging as promising biomarkers for predicting ICB response. Early characterization of ctDNA and TCR dynamics may enable timely treatment adjustments before clinical or radiological progression.
Patients And Methods:
The IO-KIN study (NCT04606940) is a single-center, prospective trial involving 15 patients with R/M HNSCC treated with nivolumab or pembrolizumab. Blood samples (n=104) were collected across seven timepoints from baseline to day 29. ctDNA was analyzed using a personalized assay (Signatera), and peripheral TCR repertoires were profiled using CapTCR-seq in eight patients.
Results:
A decline in ctDNA after day 8 was associated with radiological response, longer progression-free survival, and a trend toward improved overall survival. TCR repertoires transiently diversified between days 8-22, with longer diversification windows in patients showing sustained ctDNA decline. Using the GLIPHII algorithm, an EBV-specific TCR signature was identified and persisted in patients with clinical benefit. Additional TCR signatures, potentially recognizing tumor-associated antigens, emerged as early as day 3 and were linked to positive outcomes.
Conclusions:
Simultaneous early monitoring of ctDNA and TCR dynamics reveals key determinants of ICB outcomes in R/M HNSCC. The transient nature of TCR diversification emphasizes the importance of precise sample timing to guide early therapeutic decisions and improve patient outcomes.
