Chong H, Hutchinson G, Hart I R, Vile R G
Department of Histopathology, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, London, UK.
Br J Cancer. 1998 Oct;78(8):1043-50. doi: 10.1038/bjc.1998.625.
In an attempt to enhance the anti-tumour immune response, the co-stimulatory molecules B7-1 or B7-2 were expressed on the surface of B16 melanoma cells. B7-expressing tumours grew more slowly in both syngeneic immunocompetent mice and athymic T cell-immunodeficient nude mice. The delay in growth of B7-expressing tumours was dependent on natural killer (NK) cells, as reductions in tumour growth rates were minimized in mice depleted of NK cells. Systemic immunity to B16 melanoma was examined by vaccination with irradiated tumour cells. Inoculation with irradiated B16 B7-1 cells failed to protect against a subsequent challenge with live parental B16 cells, but conferred partial protection against challenge with live B16 B7-1 cells. In contrast to the local anti-tumour reaction, this protective response was dependent on T cells. The results presented here reveal some of the mechanisms involved in the in vivo response to a poorly immunogenic tumour modified to express co-stimulatory molecules.
为增强抗肿瘤免疫反应,共刺激分子B7-1或B7-2在B16黑色素瘤细胞表面表达。在同基因免疫活性小鼠和无胸腺T细胞免疫缺陷裸鼠中,表达B7的肿瘤生长均较为缓慢。表达B7的肿瘤生长延迟依赖于自然杀伤(NK)细胞,因为在NK细胞耗竭的小鼠中,肿瘤生长速率的降低最小化。通过用辐照肿瘤细胞进行疫苗接种来检测对B16黑色素瘤的全身免疫。接种辐照的B16 B7-1细胞未能预防随后活的亲代B16细胞的攻击,但对活的B16 B7-1细胞的攻击提供了部分保护。与局部抗肿瘤反应相反,这种保护性反应依赖于T细胞。此处呈现的结果揭示了体内对经修饰以表达共刺激分子的低免疫原性肿瘤的反应所涉及的一些机制。