Sojka D K, La Motte R N, Mokyr M B
Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 60612, USA.
Cancer Immunol Immunother. 2000 Apr;49(1):10-22. doi: 10.1007/s002620050022.
We have previously shown that B7-2 (CD86) and, to a lesser extent, B7-1 (CD80) contribute to the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor under conditions that lead to the acquisition of potent cytotoxic T lymphocyte (CTL) activity at the tumor site. Since B7-1 and B7-2 are expressed on both tumor cells and host antigen-presenting cells (APC), the current studies were undertaken to examine the relative importance of each costimulatory molecule on tumor cells and on host APC for the acquisition of anti-MOPC-315 CTL activity. Utilizing an in vitro system for the acquisition of CTL activity, we found that B7 expression on host APC is important for the development of CTL activity in stimulation cultures of spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers, although the expression of either B7-1 or B7-2 is sufficient. In addition, we found that B7-2, which is expressed at high levels on stimulator tumor cells, but not B7-1, which is expressed at much lower levels, is also important for the acquisition of CTL activity. However, the vast majority of the CTL activity acquired in vitro in response to stimulation with the B7-2-expressing MOPC-315 tumor cells was found to depend on B7-expressing host APC. Thus, it is likely that B7-2, which is expressed at high levels on MOPC-315 tumor cells, promotes the rapid lysis of MOPC-315 stimulator tumor cells, thereby making tumor-associated antigens more readily available for efficient presentation by B7-expressing host APC which, in turn, stimulate the acquisition of CTL activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers.
我们之前已经表明,B7-2(CD86)以及在较小程度上的B7-1(CD80),在导致肿瘤部位获得强效细胞毒性T淋巴细胞(CTL)活性的条件下,对携带大的MOPC-315肿瘤的小鼠使用低剂量美法仑(L-苯丙氨酸氮芥)的治疗效果有贡献。由于B7-1和B7-2在肿瘤细胞和宿主抗原呈递细胞(APC)上均有表达,因此进行了当前研究,以检查每种共刺激分子在肿瘤细胞和宿主APC上对于获得抗MOPC-315 CTL活性的相对重要性。利用体外获得CTL活性的系统,我们发现宿主APC上的B7表达对于低剂量美法仑治疗的MOPC-315肿瘤携带者脾细胞刺激培养物中CTL活性的发展很重要,尽管B7-1或B7-2的表达就足够了。此外,我们发现,在刺激肿瘤细胞上高水平表达的B7-2,而不是表达水平低得多的B7-1,对于获得CTL活性也很重要。然而,发现体外响应表达B7-2的MOPC-315肿瘤细胞刺激而获得的绝大多数CTL活性依赖于表达B7的宿主APC。因此,很可能在MOPC-315肿瘤细胞上高水平表达的B7-2促进了MOPC-315刺激肿瘤细胞的快速裂解,从而使肿瘤相关抗原更易于被表达B7的宿主APC有效呈递,进而刺激来自低剂量美法仑治疗的MOPC-315肿瘤携带者脾细胞获得CTL活性。