Dasgupta Santanu, Bhattacharya-Chatterjee Malaya, O'Malley Bert W, Chatterjee Sunil K
Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA.
J Immunol. 2005 Oct 15;175(8):5541-50. doi: 10.4049/jimmunol.175.8.5541.
In an orthotopic murine model of head and neck squamous cell carcinoma (SCC VII/SF) we studied NK cell-mediated immunity following vaccination with a recombinant vaccinia virus expressing IL-2 (rvv-IL-2). SCC VII/SF tumor cells were injected into the oral cavity of C3H/HeJ mice on day 0. Mice were vaccinated on days 7, 10, and 14 with rvv-IL-2 and control vaccines. Phenotypes, numbers, and biological activities of NK cells were determined following vaccination. Levels of expression of NK-activating receptor NKG2D and CD16 on NK cell surface were assayed in the vaccinated mice. Expression of NKG2D ligands, Rae1, and H60 on SCC VII/SF cells was also examined. Vaccination with rvv-IL-2 resulted in expansion of NK cells. NK cells isolated from rvv-IL-2-vaccinated mice had significantly higher biological activities compared with mice treated with control vaccines. NK cells from tumor-bearing mice expressed significantly lower levels of NKG2D and CD16 compared with rvv-IL-2 vaccinated mice. SCC VII/SF tumors expressed NKG2D ligand Rae 1, although H60 was not present. SCC VII/SF tumors expressed high levels of TGF-beta1, which were down-modulated by vaccination with rvv-IL-2. Incubation of NK cells with tumor homogenate or cultured supernatant of SCC VII/SF cells reduced the expression of NKG2D and CD16. This inhibition appeared to be mediated by TGF-beta1. SCC VII/SF tumors in the oral cavity of the mice secrete high quantities of TGF-beta1, which reduce the expression of NK cell receptor NKG2D as well as CD16 and inhibits biological functions of NK cells.
在头颈部鳞状细胞癌的原位小鼠模型（SCC VII/SF）中，我们研究了用表达白细胞介素-2的重组痘苗病毒（rvv-IL-2）接种后自然杀伤（NK）细胞介导的免疫反应。在第0天，将SCC VII/SF肿瘤细胞注射到C3H/HeJ小鼠的口腔中。在第7、10和14天，用rvv-IL-2和对照疫苗对小鼠进行接种。接种后测定NK细胞的表型、数量和生物学活性。在接种疫苗的小鼠中检测NK细胞表面NK激活受体NKG2D和CD16的表达水平。还检测了SCC VII/SF细胞上NKG2D配体Rae1和H60的表达。用rvv-IL-2接种导致NK细胞扩增。与用对照疫苗处理的小鼠相比，从用rvv-IL-2接种的小鼠中分离出的NK细胞具有显著更高的生物学活性。与用rvv-IL-2接种的小鼠相比，荷瘤小鼠的NK细胞表达的NKG2D和CD16水平显著降低。SCC VII/SF肿瘤表达NKG2D配体Rae 1，但不存在H60。SCC VII/SF肿瘤表达高水平的转化生长因子-β1（TGF-β1），用rvv-IL-2接种可下调其水平。用肿瘤匀浆或SCC VII/SF细胞的培养上清液孵育NK细胞可降低NKG2D和CD16的表达。这种抑制似乎是由TGF-β1介导的。小鼠口腔中的SCC VII/SF肿瘤分泌大量TGF-β1，其降低NK细胞受体NKG2D以及CD16的表达，并抑制NK细胞的生物学功能。
