Effect of human natural killer and γδ T cells on the growth of human autologous melanoma xenografts in SCID mice
Effect of human natural killer and γδ T cells on the growth of human autologous melanoma xenografts in SCID mice
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DOI：
10.1158/0008-5472.can-03-1501
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发表时间：
2004-01-01
期刊：
影响因子：
11.2
通讯作者：
Fais, S
中科院分区：
文献类型：
--
作者：
Lozupone, F;Pende, D;Fais, S
自然杀伤(NK)细胞首次被鉴定为在体外杀死不同来源的肿瘤细胞的能力。同样，Gammadelta T淋巴细胞对各种肿瘤细胞株显示出很强的细胞毒活性。然而，NK细胞和Gammadelta细胞在体内介导针对人类恶性肿瘤的自然免疫反应的能力仍然不清楚。严重联合免疫缺陷(SCID)小鼠已成功地移植了人类肿瘤。本研究探讨了NK细胞、Vdelta1或Vdelta2γ/Delta T淋巴细胞局部和全身治疗对自体黑色素瘤细胞的体内抗肿瘤作用。结果表明，当肿瘤细胞和淋巴样细胞都是S.C.时，这三个群体都能有效地防止自体人类黑色素瘤的生长。在同一地点接种。然而，静脉输注淋巴样细胞时，只有NK细胞和Vdelta1γ/Delta T淋巴细胞能预防或抑制S.C.自体黑色素瘤的生长。相应地，在S.C.可检测到NK细胞和VDelta Gammadelta T淋巴细胞。肿瘤部位。相反，Vdelta2 Gammadelta T淋巴细胞仅在SCID小鼠的脾中检测到。此外，即使在停止治疗后，NK细胞仍保持对肿瘤生长的抑制作用。事实上，它们在肿瘤部位存在的时间更长。这些数据支持在肿瘤免疫治疗中利用NK细胞和Vdelta1 Gammadelta T淋巴细胞的可能性。此外，我们的研究强调了人类肿瘤/SCID小鼠模型在针对人类肿瘤的免疫治疗方案的临床前评估中的有效性。
Natural killer (NK) cells were first identified for their ability to kill tumor cells of different origin in vitro. Similarly, gammadelta T lymphocytes display strong cytotoxic activity against various tumor cell lines. However, the ability of both the NK and gammadelta cells to mediate natural immune response against human malignant tumors in vivo is still poorly defined. Severe combined immunodeficient (SCID) mice have been successfully engrafted with human tumors. In this study, the antitumor effect of local as well as of systemic treatments based on NK cells or Vdelta1 or Vdelta2 gamma/delta T lymphocytes against autologous melanoma cells was investigated in vivo. The results show that all three of the populations were effective in preventing growth of autologous human melanomas when both tumor and lymphoid cells were s.c. inoculated at the same site. However, when lymphoid cells were infused i.v., only NK cells and Vdelta1 gamma/delta T lymphocytes could either prevent or inhibit the s.c. growth of autologous melanoma. Accordingly, both NK cells and Vdelta gammadelta T lymphocytes could be detected at the s.c. tumor site. In contrast, Vdelta2 gammadelta T lymphocytes were only detectable in the spleen of the SCID mice. Moreover, NK cells maintained their inhibitory effect on tumor growth even after discontinuation of the treatment. Indeed they were present at the tumor site for a longer period.These data support the possibility to exploit NK cells and Vdelta1 gammadelta T lymphocytes in tumor immunotherapy. Moreover, our study emphasizes the usefulness of human tumor/SCID mouse models for preclinical evaluation of immunotherapy protocols against human tumors.