Yang Wuwei, Wang Wei, Liu Bing, Zhu Baorang, Li Jing, Xu Debao, Ni Yanli, Bai Li, Liu Guangxian
Cancer Therapy Center, Affiliated Hospital of the Academy of Military Medical Sciences, Beijing, China.
Asia Pac J Clin Oncol. 2018 Oct;14(5):e490-e497. doi: 10.1111/ajco.12836. Epub 2018 Jan 8.
Thermal ablation therapy has recently emerged as a promising noninvasive treatment modality for localized solid malignancies. Except its direct tumor-cell-killing effect on local tumor tissues, the immunomodulatory effect has also long been noticed which too has substantial effect on clinical outcome, but it is complicated. Though much has been investigated and rich evidences have been achieved, the fundamental state and profile of immunomodulation by thermal ablation in cancer patients, its exact mechanism, especially the systematic mechanism, and its effect on antitumor immunity remain unclear.
In this study, we dynamically monitored the immunomodulation by thermal ablation through combined analysis of peripheral lymphocyte populations, functional T cell subtype Th1 (CD3+CD4+IFN-r+), Th2 (CD3+CD4+IL-4+), Tc1 (CD3+CD8+IFN-r+), Tc2 (CD3+CD8+IL-4+) and mRNA expression of several immune-active and -suppressive molecules including CD25, CD28, cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1, Foxp3, transforming growth factor beta (TGF-β) and interleukin (IL-10) in 16 cancer patients.
The results show that local cancer thermal ablation modulated the cellular immunity characterized by obviously downregulation of regulatory T cells (Treg) and cytotoxicity T cells followed by CD4, CD8 and suppressor T cells (Ts), but upregulation of natural killer (NK) cells and mRNA expression of TGF-β and IL-10, suggesting a slight inhibition of the cellular immunity which may affect antitumor immunity.
We suggest a further immunomodulation therapy after thermal therapy for recovering a Th1- and Tc1-dominant immune response for pursuing a better long-term antitumor immunity.
热消融治疗最近已成为一种有前景的局部实体恶性肿瘤无创治疗方式。除了其对局部肿瘤组织的直接肿瘤细胞杀伤作用外，免疫调节作用也早已被注意到，这对临床结果也有重大影响，但情况复杂。尽管已经进行了大量研究并取得了丰富证据，但癌症患者热消融免疫调节的基本状态和特征、其确切机制，尤其是系统机制以及对抗肿瘤免疫的影响仍不清楚。
在本研究中，我们通过联合分析16例癌症患者外周淋巴细胞群体、功能性T细胞亚群Th1（CD3 + CD4 + IFN - r +）、Th2（CD3 + CD4 + IL - 4 +）、Tc1（CD3 + CD8 + IFN - r +）、Tc2（CD3 + CD8 + IL - 4 +）以及包括CD25、CD28、细胞毒性T淋巴细胞相关蛋白4、程序性细胞死亡蛋白1、Foxp3、转化生长因子β（TGF - β）和白细胞介素（IL - 10）在内的几种免疫活性和抑制分子的mRNA表达，动态监测热消融的免疫调节作用。
结果表明，局部癌症热消融调节了细胞免疫，其特征为调节性T细胞（Treg）和细胞毒性T细胞明显下调，随后是CD4、CD8和抑制性T细胞（Ts），但自然杀伤（NK）细胞以及TGF - β和IL - 10的mRNA表达上调，提示细胞免疫受到轻微抑制，这可能影响抗肿瘤免疫。
我们建议热疗后进一步进行免疫调节治疗，以恢复以Th1和Tc1为主导的免疫反应，从而获得更好的长期抗肿瘤免疫力。
