Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells
Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells
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DOI：
10.1111/j.1349-7006.2006.00319.x
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发表时间：
2006-12-01
期刊：
影响因子：
5.7
通讯作者：
Yamamoto, Naoki
中科院分区：
文献类型：
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作者：
Dewan, Md. Zahidunnabi;Terunuma, Hiroshi;Yamamoto, Naoki
自然杀伤(NK)细胞是抵抗微生物感染和肿瘤的先天免疫反应的重要组成部分。NK细胞在肿瘤生长和侵袭中的直接作用尚不清楚。NOD/SCID/Gamma c(Null)(NOG)基因敲除的NOD/SCID/Gamma c(Null)(NOG)小鼠，原发渗出性淋巴瘤(PEL)细胞在3周内能高效地产生肿瘤和腹水，并在不同的器官中渗透。相比之下，在带有NK细胞的T和B细胞敲除NOD/SCID小鼠中，PEL细胞在接种部位形成小肿瘤，但完全无法渗透到各种器官。与未治疗的NOD/SCID小鼠相比，体内瞬时消除NK细胞活性的抗尿TM-β1抗体对NOD/SCID小鼠的免疫抑制导致了肿瘤致瘤性和器官侵袭的增强。活化的人NK细胞抑制NOG小鼠肿瘤的生长和侵袭。我们的结果表明，NK细胞在PEL细胞的生长和渗透中起着重要作用，活化的NK细胞无论是单独还是与常规治疗相结合，都可能成为抗肿瘤或病毒感染细胞的一种有前途的免疫治疗工具。PEL细胞在NOG小鼠体内的快速高效植入也表明，这种新的动物模型可能为了解和研究NOG的发病机制和恶性细胞生长机制提供了一个独特的机会。
Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gamma c(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta 1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.