Purpose: We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer(AGC) and the role of mutational analysis of circulating tumor DNA(ctDNA) and T cell receptor (TCR) repertoire in predicting clinical outcomes. Experimental Design: Consecutive patients (n=63) with advanced gastric cancer were allocated to treatment with S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 or DC-CIK combined with S-1 plus cisplatin. The primary endpoints were progression-free survival (PFS) and overall survival (OS) at 1 year; the secondary endpoints were disease control rate and analysis of ctDNA and TCR repertoire. Results: The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR+PR+SD) were 5.6%, 33.3%, 47.1% and 76.9% in the S-1 alone, the S-1 plus cisplatin, DC-CIK combined with S-1 and DC-CIK combined with the S-1 plus cisplatin groups respectively (P=0.001). After adjusting for competing risk factors, treatment with DC-CIK combined with S-1 plus cisplatin was confirmed to be an independent predictor of PFS and OS (P=0.001). A decrease in the frequency and number of mutations in ctDNA was observed in 19 patients (63.3%) following the DC-CIK infusions. Decreased ctDNA mutational frequency and restored TCR repertoire were associated with improved PFS and OS (P =0.001). Conclusion: DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.
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