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

• S. Ji ^[1] ; J. Li ^[2] ; L. Chang ^[2] ; C. Zhao ^[3] ; R. Jia ^[3] ; Z. Tan ^[3] ; R. Liu ^[3] ; Y. Zhang ^[3] ; Y. Li ^[3]
  1. [1] Academy of Military Medical Sciences

     Academy of Military Medical Sciences

     China

     
  2. [2] Geneplus-Beijing Institute, Beijing, China
  3. [3] Department of Gastrointestinal Oncology, The Fifth Medical Centre, Chinese PLA General Hospital, No. 8 East Street, Fengtai District, Beijing 100071, China

  Mostrar afiliaciones +
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 23, Nº. 8, 2021, págs. 1646-1656
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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