Resumen de Peripheral blood T‑cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD‑1 inhibitor

S. Ji, J. Li, L. Chang, C. Zhao, R. Jia, Z. Tan, R. Liu, Y. Zhang, Y. Li

• Background Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains signifcant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy.

  Methods 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita’s overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples.

  Results Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy.

  In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a signifcantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confdence interval [CI] 1.14–13.48; P=0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16–3.79; P=0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49–8.38; P=0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98;

  95% CI 4.37–44.68; P<0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22–7.03; P=0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratifcation in a pooled cohort.

  Conclusion The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers