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• W4323660481 abstract "Abstract Background Immune checkpoint inhibitors (ICIs) have significant clinical benefit for a subset of patients with gastrointestinal cancers including esophageal cancer, gastric cancer and colorectal cancer. However, it is difficult to predict which patients will respond to immune therapy or induce immune-related adverse events (irAEs). This study was initiated to determine if peripheral T-cell receptor (TCR) repertoire profiling could predict the clinical efficacy of anti-PD-1 treatment, while also predict adverse events. Methods Blood samples from 31 patients with GICs were collected before anti-PD-1 antibody treatment initiation. The clinical significance of TCR repertoire profiling from PBMCs was evaluated in all the enrolled patients. A highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The performance of the nomogram was assessed by receiver operating characteristic (ROC) curve, concordance index (C-index), and calibration curves, and decision curve analysis (DCA) was used to assess its clinical applicability. Results Compared to non-responders (PD), the DE50 scores were significantly higher in responders (SD and PR) (P = 0.018). There was a trend that higher DE50 at baseline was associated with the occurrence of adverse events, but it did not reach statistical significance (P = 0.1779). Patients with a high DE50 score showed better progression-free survival (PFS) than those with a low DE50 score (P = 0.0022). The multivariable Cox regression demonstrated that high DE50 and low PLR were significant independent predictors for better PFS when treated with anti-PD-1 antibody. Furthermore, a highly predictive nomogram was set up based on peripheral TCR repertoire profiling. The AUCs of this system at 3-, 6- and 12-month PFS reached 0.825, 0.802, and 0.954, respectively. The nomogram had a C-index of 0.768 (95% CI: 0.879 − 0.658). Meanwhile, the calibration curves also demonstrated the reliability and stability of the model. Conclusions High DE50 scores were predictive of a favorable response and longer PFS to anti-PD-1 treatment in GIC patients. The nomogram based on TCR repertoire profiling was a reliable and practical tool, which could provide risk assessment and clinical decision-making for individualized treatment of patients." @default.
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• W4323660481 date "2023-03-09" @default.
• W4323660481 modified "2023-10-17" @default.
• W4323660481 title "Clinical significance of peripheral TCR repertoire profiling and individualized nomograms in patients with gastrointestinal cancer treated with anti-PD-1 antibody" @default.
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• W4323660481 doi "https://doi.org/10.21203/rs.3.rs-2551844/v1" @default.
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