Early activation and interferon-γ production of tumor-infiltrating mature CD27high natural killer cells
Early activation and interferon-γ production of tumor-infiltrating mature CD27high natural killer cells
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DOI：
10.1111/j.1349-7006.2011.02042.x
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发表时间：
2011-11-01
期刊：
影响因子：
5.7
通讯作者：
Irimura, Tatsuro
中科院分区：
文献类型：
--
作者：
Hayakawa, Yoshihiro;Sato-Matsushita, Marimo;Irimura, Tatsuro
已知自然杀伤（NK）细胞通过其直接的细胞毒性功能关键地参与肿瘤的控制，但也已被提议作为引发随后的适应性肿瘤特异性免疫应答的干扰素（IFN）-γ的初始来源。尽管越来越多的证据支持NK细胞在抗肿瘤免疫应答中的重要性，但NK细胞浸润肿瘤微环境的免疫学特征和调节该过程的机制仍不清楚。在本研究中，我们发现NK细胞浸润早期发育的MCA 205肿瘤，并进一步表明成熟的CD 27（高）NK细胞是NK细胞在肿瘤微环境中积累的主要亚群。肿瘤浸润性NK细胞显示出活化的细胞表面表型，并提供了IFN-γ的早期来源。重要的是，我们还发现，宿主IFN-γ对于NK细胞浸润到局部肿瘤部位至关重要，并且肿瘤浸润NK细胞主要通过IFN-γ途径抑制肿瘤生长。这项工作暗示了IFN-γ作为NK细胞募集到肿瘤微环境中的正调节因子和有效的抗肿瘤免疫效应应答的重要性。（Cancer Sci 2011; 102：1967-1971）
Natural killer (NK) cells are known to be critically involved in the control of tumors through their direct cytotoxic function, but have also been proposed as an initial source of interferon (IFN)-gamma that primes subsequent adaptive tumor-specific immune responses. Although mounting evidence supports the importance of NK cells in antitumor immune responses, the immunological characteristics of NK cells infiltrating the tumor microenvironment and the mechanisms that regulate this process remain unclear. In the present study, we found that NK cells infiltrate early developing MCA205 tumors, and further showed that mature CD27(high) NK cells were the predominant subpopulation of NK cells accumulating in the tumor microenvironment. The tumor-infiltrating NK cells displayed an activated cell surface phenotype and provided an early source of IFN-gamma. Importantly, we also found that host IFN-gamma was critical for NK cell infiltration into the local tumor site and that the tumor-infiltrating NK cells mainly suppressed tumor growth via the IFN-gamma pathway. This work implicates the importance of IFN-gamma as a positive regulatory factor for NK cell recruitment into the tumor microenvironment and an effective antitumor immune effector response. (Cancer Sci 2011; 102: 1967-1971)