Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor
Clin. transl. oncol. (Print)
; 23(8): 1646-1656, ago. 2021.
Article
in En
| IBECS
| ID: ibc-222163
Responsible library:
ES1.1
Localization: ES15.1 - BNCS
ABSTRACT
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 significant. 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 Morisitas 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 significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.1413.48; P = 0.030) and a longer progression-free survival (PFS) (median 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.163.79; P = 0.014) and overall survival (OS) (median NA vs. 8.97 months; HR 3.53; 95% CI 1.498.38; 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 4.3744.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.227.03; 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 stratification 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 (AU)
Key words
Full text:
1
Collection:
06-national
/
ES
Database:
IBECS
Main subject:
Receptors, Antigen, T-Cell
/
Immunotherapy, Adoptive
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Antineoplastic Agents, Immunological
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Gastrointestinal Neoplasms
Limits:
Adult
/
Aged
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Female
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Humans
/
Male
Language:
En
Journal:
Clin. transl. oncol. (Print)
Year:
2021
Document type:
Article