Department of Biochemistry, Wannan Medical College, Wuhu, Anhui 241002, PR China; Anhui Province Key Laboratory of Active Biological Macro-molecules, Wannan Medical College, Wuhu, Anhui 241002, PR China.
Department of Gynaecology and Obstetrics, Traditional Chinese Medical Hospital of Wuhu, Wuhu, Anhui 241000, PR China.
Int Immunopharmacol. 2018 Feb;55:306-311. doi: 10.1016/j.intimp.2017.12.029. Epub 2018 Jan 5.
In a previous study, we constructed a MHSP65-TCL anti-lung cancer vaccine with Lewis lung carcinoma TCL plus MHSP65, and illustrated its anti-lung cancer effect through specific and nonspecific anti-tumor immunity. However, TCL contains some immunoinhibit components such as FasL. If this component can be eliminated from TCL, the anti-tumor immunity of MHSP65-TCL constructed with TCL should be improved. In the present study, we knocked down FasL from Lewis lung carcinoma cells and prepared MHSP65-(FasL-/TCL) with this cell line's TCL. After further investigation, MHSP65-(FasL-/TCL) exhibited a better ability to reduce splenocytes apoptosis, promote its activation and secretion of secretingTNF-β, IL-2 compared with MHSP65-(FasL+/TCL). Accordingly, specific and nonspecific antitumor immunity induced by MHSP65-(FasL-/TCL) is stronger than that of MHSP65-(FasL+/TCL). In vivo, MHSP65-(FasL-/TCL) immunization can prolong survival of Lewis lung carcinoma bearing mice. Thus, we report that the anti-lung cancer effect of MHSP65-TCL can be improved by removal of FasL from the TCL. It provides a new route to construct MHSP65-TCL and other antitumor vaccines based on TCL.
在之前的研究中,我们构建了一种 MHSP65-TCL 抗肺癌疫苗,使用 Lewis 肺癌 TCL 加 MHSP65,通过特异性和非特异性抗肿瘤免疫来阐明其抗肺癌作用。然而,TCL 中含有一些免疫抑制成分,如 FasL。如果能从 TCL 中消除这种成分,用 TCL 构建的 MHSP65-TCL 的抗肿瘤免疫应该会得到改善。在本研究中,我们从 Lewis 肺癌细胞中敲除了 FasL,并使用该细胞系的 TCL 制备了 MHSP65-(FasL-/TCL)。进一步研究表明,MHSP65-(FasL-/TCL)在降低脾细胞凋亡、促进其活化和分泌 TNF-β、IL-2 方面的能力优于 MHSP65-(FasL+/TCL)。因此,MHSP65-(FasL-/TCL)诱导的特异性和非特异性抗肿瘤免疫比 MHSP65-(FasL+/TCL)更强。在体内,MHSP65-(FasL-/TCL)免疫可以延长 Lewis 肺癌荷瘤小鼠的生存时间。因此,我们报告说,从 TCL 中去除 FasL 可以提高 MHSP65-TCL 的抗肺癌作用。它为构建基于 TCL 的 MHSP65-TCL 和其他抗肿瘤疫苗提供了一条新途径。