Martin B K, Frelinger J G, Ting J P
Lineberger Comprehensive Cancer Center, Department of Microbiology-Immunology, University of North Carolina at Chapel Hill 27599, USA.
J Immunol. 1999 Jun 1;162(11):6663-70.
Early reports suggest that the costimulatory molecule CD86 (B7-2) has sporadic efficacy in tumor immunity, whereas changes in cancer immunity mediated by the MHC class II transactivator (CIITA) have not been extensively investigated. CIITA activates MHC class II expression in most cells; however, in the Line 1 lung carcinoma model system, CIITA activates MHC class I and well as class II. Here we show that CD86 is very effective in inducing a primary immune response against Line 1. Tumor cells expressing CD86 grew in only 50% of the mice injected with live cells, and those mice that developed tumors did so with significantly delayed kinetics. Furthermore, irradiated CD86-expressing Line 1 cells served as an effective tumor vaccine, demonstrating that CD86 is effective in inducing tumor immunity in the Line 1 system. These data suggest that if CIITA and CD86 cooperate, enhanced tumor immunity could be achieved. CIITA alone was mildly beneficial in slowing primary tumor growth but only when expressed at low levels. Clones expressing high levels of class II MHC grew as fast as or faster than parental tumor, and CIITA expression in a tumor vaccine assay lacked efficacy. When CIITA and CD86 were coexpressed, there was no cooperative immune protection from tumor growth. Cells that coexpress both genes also failed as a cancer vaccine, suggesting a negative role for CIITA in this lung carcinoma. These data suggest that human cancer vaccine trials utilizing CIITA gene therapy alone or in combination with CD86 should be approached with caution.
早期报告显示，共刺激分子CD86（B7-2）在肿瘤免疫中具有散发性疗效，而由MHC II类反式激活因子（CIITA）介导的癌症免疫变化尚未得到广泛研究。CIITA在大多数细胞中激活MHC II类表达；然而，在1号线肺癌模型系统中，CIITA激活MHC I类以及II类。在此我们表明，CD86在诱导针对1号线的初次免疫反应中非常有效。表达CD86的肿瘤细胞在注射活细胞的小鼠中只有50%生长，而那些长出肿瘤的小鼠其肿瘤生长动力学明显延迟。此外，经照射的表达CD86的1号线细胞可作为有效的肿瘤疫苗，表明CD86在1号线系统中诱导肿瘤免疫方面有效。这些数据表明，如果CIITA和CD86协同作用，可能实现增强的肿瘤免疫。单独的CIITA在减缓原发性肿瘤生长方面有轻微益处，但仅在低水平表达时。表达高水平II类MHC的克隆生长速度与亲本肿瘤一样快或更快，并且在肿瘤疫苗试验中CIITA表达缺乏疗效。当CIITA和CD86共表达时，没有对肿瘤生长的协同免疫保护作用。同时表达这两个基因的细胞作为癌症疫苗也失败了，表明CIITA在这种肺癌中起负面作用。这些数据表明，单独使用CIITA基因治疗或与CD86联合进行的人类癌症疫苗试验应谨慎进行。
