Mizukoshi Eishiro, Yamashita Tatsuya, Arai Kuniaki, Terashima Takeshi, Kitahara Masaaki, Nakagawa Hidetoshi, Iida Noriho, Fushimi Kazumi, Kaneko Shuichi
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan.
Cancer Immunol Immunother. 2016 Jun;65(6):715-25. doi: 10.1007/s00262-016-1837-2. Epub 2016 Apr 15.
Hepatic arterial infusion chemotherapy (HAIC) has been employed as an alternative therapy to sorafenib for the patients with advanced hepatocellular carcinoma (HCC). In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplatin modulated the frequencies of various immune cells. In 22.2 % of patients, the frequency of TAA-specific T cells increased after HAIC. Although the frequency of Tregs decreased after HAIC, it was not associated with the prognosis of patients. An analysis of prognostic factors for overall survival identified diameter of the tumor (<3.0 cm), absence of major portal vein invasion, absence of distant metastasis, Union Internationale Contre Le Cancer tumor lymph node metastasis stage (I or II), neutrophil lymphocytic ratio (<2.1) and the frequency of MDSCs (<30.5 %) as factors that prolonged overall survival time after HAIC. Even in the group adjusted with progressive levels of tumors, patients with a low frequency of MDSCs had a significantly longer overall survival time. In conclusion, the frequency of MDSCs before the treatment is a prognostic factor in HAIC against HCC.
肝动脉灌注化疗(HAIC)已被用作晚期肝细胞癌(HCC)患者索拉非尼的替代治疗方法。在本研究中,我们对接受HAIC治疗的晚期HCC患者的各种免疫细胞反应进行了比较分析,包括肿瘤相关抗原(TAA)特异性T细胞、调节性T细胞(Tregs)和骨髓来源的抑制细胞(MDSCs)。该研究共检查了36例HCC患者。采用干扰素γ酶联免疫斑点试验检测TAA特异性T细胞的频率。通过多色荧光激活细胞分选分析检测Tregs和MDSCs的频率。使用干扰素(IFN)/5-氟尿嘧啶(FU)或IFN/FU +顺铂进行的HAIC治疗调节了各种免疫细胞的频率。在22.2%的患者中,HAIC后TAA特异性T细胞的频率增加。虽然HAIC后Tregs的频率降低,但这与患者的预后无关。对总生存预后因素的分析确定,肿瘤直径(<3.0 cm)、无主要门静脉侵犯、无远处转移、国际抗癌联盟肿瘤淋巴结转移分期(I或II)、中性粒细胞淋巴细胞比率(<2.1)和MDSCs频率(<30.5%)是HAIC后延长总生存时间的因素。即使在根据肿瘤进展程度进行调整的组中,MDSCs频率低的患者总生存时间也显著更长。总之,治疗前MDSCs的频率是HAIC治疗HCC的一个预后因素。