Qingdao Central Hospital, The Second Clinical Hospital of Qingdao University , Qingdao, China.
Cancer Biotherapy Center of Qingdao Key Lab , Qingdao, China.
Immunol Invest. 2020 Jul;49(5):522-534. doi: 10.1080/08820139.2019.1696360. Epub 2019 Dec 3.
The purpose of this study is to investigate whether the DC cells combined with CIK cells (DC/CIK) and DC activated cytotoxic T cells (DC-ACT) treatment can promote antitumor response and change the immune indicators by targeting the heterogeneous tumor cell populations at a system level.
In this study, 112 patients with cancer were assigned to the DC/CIK treatment and 116 patients received the DC-ACT therapy. We detected the lymphocyte subsets and other immune indicators pre- and post-treatment to evaluate the changes of patient's immunity and compare the differences in immune status between two adoptive cellular immunotherapies.
DC/CIK therapy elevated the percentage of CD3+ HLA-DR+ T cells, NK cells and several serological cytokines such as IL-2, IL-6 after cell infusion ( < .05). DC-ACT therapy could increase the total CD3 + T cells, CD8 + T cells, CD3+ HLA-DR+ cells and IL-12 cytokines after cell infusion ( < .05). The levels of IL-4/IFN-γ, IL-4/IL-12 and IL-6/IL-12 were reduced significantly in the DC-ACT group compared with DC/CIK group. These observations suggested that DC-ACT therapy has more dominance to induce Th1 cytokine response instead of skewing toward the Th2 cytokine profile based on the immunomodulatory properties.
These results indicated that DC, CIK, and DC-ACT cells exert anti-tumor activity through the different pathways. Thus, this work may provide valuable insights into the clinical curative effect evaluation of immunocyte therapy and the design of combined immunotherapeutic strategies for malignant tumors.
本研究旨在探讨树突状细胞(DC)与细胞因子诱导的杀伤细胞(CIK)联合(DC/CIK)和树突状细胞激活的细胞毒性 T 细胞(DC-ACT)治疗是否可以通过靶向异质性肿瘤细胞群在系统水平上促进抗肿瘤反应和改变免疫指标。
本研究将 112 例癌症患者分配至 DC/CIK 治疗组,116 例患者接受 DC-ACT 治疗。我们检测了治疗前后淋巴细胞亚群和其他免疫指标,以评估患者免疫的变化,并比较两种过继性细胞免疫治疗的免疫状态差异。
DC/CIK 治疗可在细胞输注后提高 CD3+ HLA-DR+T 细胞、NK 细胞和几种血清细胞因子(如 IL-2、IL-6)的比例(<0.05)。DC-ACT 治疗可增加细胞输注后总 CD3+T 细胞、CD8+T 细胞、CD3+HLA-DR+细胞和 IL-12 细胞因子的水平(<0.05)。与 DC/CIK 组相比,DC-ACT 组的 IL-4/IFN-γ、IL-4/IL-12 和 IL-6/IL-12 水平显著降低。这些观察结果表明,基于免疫调节特性,DC-ACT 治疗具有诱导 Th1 细胞因子反应的优势,而不是偏向 Th2 细胞因子谱。
这些结果表明,DC、CIK 和 DC-ACT 细胞通过不同途径发挥抗肿瘤活性。因此,这项工作可能为免疫细胞治疗的临床疗效评估和恶性肿瘤联合免疫治疗策略的设计提供有价值的见解。