Data from Autologous Dendritic Cell-Cytokine Induced Killer Cell Immunotherapy Combined with S-1 Plus Cisplatin in Patients with Advanced Gastric Cancer: A Prospective Study

Abstract

<div>AbstractPurpose:<p>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.</p>Patients and Methods:<p>Consecutive patients (<i>n</i> = 63) with AGC 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.</p>Results:<p>The DC–CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR<sup>+</sup>PR<sup>+</sup>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 (<i>P</i> = 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 (<i>P</i> = 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 (<i>P</i> = 0.001).</p>Conclusions:<p>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.</p></div>