Abstract

The two-drug combined chemotherapy of platinum and fluorouracil has been reported to efficiently kill tumor cells as the first-line treatment for advanced gastric cancer. However, the effect of these drugs on T cells remains unclear. Here, we showed that T cells including CD4⁺ T cells and CD8⁺ T cells of the patients with advanced gastric cancer after platinum and fluorouracil chemotherapy exhibited enhanced ex vivo proliferation ability as compared to that before chemotherapy. In addition, platinum and fluorouracil also promoted the differentiation of human T cells into Th1 and Th9 subtypes and cytotoxic T lymphocytes (CTLs) in vitro and in vivo. Accordingly, the combination therapy greatly suppressed tumor growth with increased tumor infiltration of Th1, Th9, and CTL cells in a mouse tumor model. Moreover, in activated T cells, long-term treatment with these two drugs further facilitates T cell activation along with promoted nuclear factor-κB (NF-κB) activation. Our findings demonstrate a previously unidentified function of platinum and fluorouracil combination chemotherapy in promoting T cell–mediated antitumor immunity.

中文翻译：

---

铂与氟尿嘧啶联合化疗促进T细胞介导的抗肿瘤免疫

 抽象的

据报道，铂和氟尿嘧啶两药联合化疗可有效杀死肿瘤细胞，作为晚期胃癌的一线治疗。然而，这些药物对 T 细胞的影响仍不清楚。在这里，我们发现晚期胃癌患者在铂类和氟尿嘧啶化疗后，与化疗前相比，T细胞（包括CD4 ⁺ T细胞和CD8 ⁺ T细胞）表现出增强的离体增殖能力。此外，铂和氟尿嘧啶还在体外和体内促进人类T细胞分化为Th1和Th9亚型以及细胞毒性T淋巴细胞（CTL）。因此，联合疗法极大地抑制了小鼠肿瘤模型中的肿瘤生长，并增加了 Th1、Th9 和 CTL 细胞的肿瘤浸润。此外，在活化的 T 细胞中，这两种药物的长期治疗进一步促进 T 细胞活化，并促进核因子-κB (NF-κB) 活化。我们的研究结果证明了铂类和氟尿嘧啶联合化疗在促进 T 细胞介导的抗肿瘤免疫方面具有先前未知的功能。