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从结核分枝杆菌青山 B 株提取的 Z-100 作为热肿瘤诱导剂的潜力

英文原题:Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer.

查看英文原题

Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer.

PubMed 2022/12/09(内容时间) Cancer Cell Int Q1 · IF 7(JCR 2025)

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中文摘要

肿瘤微环境是决定癌症免疫治疗疗效的最重要因素之一。特别是,疗效的变异性与肿瘤是热肿瘤还是冷肿瘤有关,热肿瘤表现出更强的T细胞浸润,对免疫治疗反应更好。从结核分枝杆菌青山B株中提取的Z-100已被报道可增加免疫细胞的细胞因子产生。

在本研究中,我们检测了其对肿瘤微环境的影响及其作为热肿瘤诱导剂的潜力。通过在肿瘤注射前开始给药,在小鼠口腔鳞状细胞癌(Sq-1979)肿瘤模型中证实了Z-100的抗肿瘤作用。收集治疗后的肿瘤以鉴定浸润的CD8 + T细胞。

此外,在用抗CD8抗体处理的小鼠和IL-12p40敲除(KO)小鼠中检测了Z-100的抗肿瘤作用。我们发现Z-100具有强效抗肿瘤作用,并增加了肿瘤中CD8 + T细胞的比例。

此外,浸润肿瘤的CD8 + T细胞被鉴定为效应记忆CD8 + T细胞。进一步地,Z-100的抗肿瘤作用在用抗CD8抗体处理的小鼠和IL-12p40 KO小鼠中被消除。

因此,Z-100通过增加肿瘤浸润CD8 + T细胞来诱导其抗肿瘤作用,表明Z-100可能通过作为热肿瘤诱导剂而成为一种有用的癌症治疗方法。

展开英文摘要原文

The tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells.

In this study, we examined its effect on the tumor microenvironment and its potential as a hot tumor inducer. The antitumor effect of Z-100 was confirmed in a mouse oral squamous cell carcinoma (Sq-1979) tumor model by starting administration before tumor injection. Treated tumors were collected to identify infiltrating CD8 + T cells. The antitumor effects of Z-100 were additionally examined in mice treated with anti-CD8 antibody and in IL-12p40 knockout (KO) mice.

We found that Z-100 had strong antitumor effects and increased the proportion of CD8 + T cells in tumors.

Moreover, the CD8 + T cells infiltrating tumors were identified as effector memory CD8 + T cells.

Furthermore, the antitumor effects of Z-100 were abolished in mice treated with an anti-CD8 antibody and in IL-12p40 KO mice.

Thus, Z-100 induces its antitumor effects by increasing tumor-infiltrating CD8 + T cells, suggesting that Z-100 may be a useful cancer therapy by acting as a hot tumor inducer.

论文信息

作者
Horii T、Orikawa Y、Ohira Y、Eta R、Kobayashi N、Sato T、Watanabe T、Tanaka T
单位
Central Research Laboratories, Zeria Pharmaceutical Co., Ltd., 2512-1, Numagami, Oshikiri, Kumagaya, Saitama, 360-0111, Japan. takayuki-horii@zeria.co.jp.Japan
期刊
Cancer cell international2022 Dec 9
原文标识
PubMed 36494701 · DOI 10.1186/s12935-022-02821-6