Lymphotactin expression by engineered myeloma cells drives tumor regression:: Mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor
Lymphotactin expression by engineered myeloma cells drives tumor regression:: Mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor
复制标题
DOI：
10.4049/jimmunol.167.1.57
复制
发表时间：
2001-07-01
影响因子：
4.4
通讯作者：
Xiang, J
中科院分区：
文献类型：
--
作者：
Cairns, CM;Gordon, JR;Xiang, J
C 趋化因子淋巴趋化素已被定性为体外和体内 T 细胞趋化剂。为了确定肿瘤内淋巴趋化素的表达是否会影响肿瘤生长，我们将淋巴趋化素的表达载体转染至SP2/0骨髓瘤细胞中，并测试其在BALB/c和裸鼠中形成肿瘤的能力。转染不会改变体外细胞的生长。尽管 SP2/0 细胞的肿瘤发生率为 100%，但 BALB/c 小鼠中表达淋巴趋化素的 SP2/0-Lptn 肿瘤总是消退，并被 CD4(+) 和 CD8(+) T 细胞和中性粒细胞浸润。 SP2/0-Lptn肿瘤的消退与I型细胞因子反应相关，并且依赖于CD4(+)和CD8(+)T细胞，但不依赖于NK细胞。 SP2/0 和 SP2/0-Lptn 肿瘤均在裸鼠中生长，但后者肿瘤的生长迟缓，并与重度中性粒细胞反应相关；这种 SP2/0-Lptn 肿瘤生长的延迟可通过小鼠的中性粒细胞耗竭而逆转。我们的数据还表明，小鼠中性粒细胞表达淋巴趋化素受体 XCR1，并且淋巴趋化素在体外特异性地化学吸引这些细胞。因此，淋巴趋化素具有天然佐剂活性，可以通过对 T 细胞和中性粒细胞的作用来增强抗肿瘤反应，因此在某些癌症的基因转移免疫疗法中可能很重要。
The C chemokine lymphotactin has been characterized as a T cell chemoattractant both in vitro and in vivo. To determine whether lymphotactin expression within tumors could influence tumor growth, we transfected an expression vector for lymphotactin into SP2/0 myeloma cells and tested their ability to form tumors in BALB/c and nude mice. Transfection did not alter cell growth in vitro. Whereas SP2/0 cells gave rise to a 100% tumor incidence, lymphotactin-expressing SP2/0-Lptn tumors invariably regressed in BALB/c mice and became infiltrated with CD4(+) and CD8(+) T cells and neutrophils. Regression of the SP2/0-Lptn tumors was associated with a type I cytokine response and dependent on both CD4(+) and CD8(+) T cells, but not NK cells. Both SP2/0 and SP2/0-Lptn tumors grew in nude mice, but growth of the latter tumors was retarded and associated with heavy neutrophil responses; this retardation of SP2/0-Lptn tumor growth was reversed by neutrophil depletion of the mice. Our data also indicate that mouse neutrophils express the lymphotactin receptor XCR1 and that lymphotactin specifically chemoattracts these cells in vitro. Thus, lymphotactin has natural adjuvant activities that may augment antitumor responses via effects on both T cells and neutrophils and thereby could be important in gene transfer immunotherapies for some cancers.