Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model.
Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model.
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DOI：
10.1038/s41598-021-84270-1
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发表时间：
2021-03-04
影响因子：
4.6
通讯作者：
Busson P
中科院分区：
文献类型：
--
作者：
Baloche V;Rivière J;Tran TBT;Gelin A;Bawa O;Signolle N;Diop MBK;Dessen P;Beq S;David M;Busson P
肿瘤免疫逃逸的机制相当多样，需要在同基因肿瘤模型中探索特定的方法。在一些人类恶性肿瘤中，Galectin-9(GAL-9)被怀疑有助于免疫逃逸。然而，与对浸润性细胞所做的研究相反，恶性细胞产生的GAL-9的贡献从未在动物模型中得到证实。因此，我们从MB49小鼠膀胱癌细胞系中获得了GAL-9阳性或阴性的等基因克隆。当GAL-9-KO细胞被连续移植到同基因小鼠体内时，观察到肿瘤生长的进行性和持续性的减少。相反，在并行连续移植到裸鼠体内的过程中，肿瘤的生长没有受到影响，从而将肿瘤抑制与增强对Gal-9-KO肿瘤的免疫反应联系起来。这种更强的免疫反应至少部分是通过改变对干扰素-γ的反应模式来解释的。一个始终如一的变化是CXCL10的产生更加丰富，这是一种主要的炎症因子，其产生通常由干扰素-γ诱导。总体而言，这些观察首次表明，在同基因小鼠体内进行连续移植对于探索肿瘤免疫逃逸的新机制是一种有价值的实验方法。
Mechanisms of tumor immune escape are quite diverse and require specific approaches for their exploration in syngeneic tumor models. In several human malignancies, galectin-9 (gal-9) is suspected to contribute to the immune escape. However, in contrast with what has been done for the infiltrating cells, the contribution of gal-9 produced by malignant cells has never been demonstrated in an animal model. Therefore, we derived isogenic clones—either positive or negative for gal-9—from the MB49 murine bladder carcinoma cell line. A progressive and consistent reduction of tumor growth was observed when gal-9-KO cells were subjected to serial transplantations into syngeneic mice. In contrast, tumor growth was unaffected during parallel serial transplantations into nude mice, thus linking tumor inhibition to the enhancement of the immune response against gal-9-KO tumors. This stronger immune response was at least in part explained by changing patterns of response to interferon-γ. One consistent change was a more abundant production of CXCL10, a major inflammatory factor whose production is often induced by interferon-γ. Overall, these observations demonstrate for the first time that serial transplantation into syngeneic mice can be a valuable experimental approach for the exploration of novel mechanisms of tumor immune escape.
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DOI：
10.1002/path.5093
发表时间：
2018-08
期刊：
The Journal of pathology
影响因子：
--
作者：
Enninga EAL;Chatzopoulos K;Butterfield JT;Sutor SL;Leontovich AA;Nevala WK;Flotte TJ;Markovic SN
通讯作者：
Markovic SN
影响因子：
3.7
作者：
Oomizu S;Arikawa T;Niki T;Kadowaki T;Ueno M;Nishi N;Yamauchi A;Hattori T;Masaki T;Hirashima M
通讯作者：
Hirashima M
影响因子：
46.9
作者：
Risso, Davide;Ngai, John;Speed, Terence P.;Dudoit, Sandrine
通讯作者：
Dudoit, Sandrine
影响因子：
5.8
作者：
Wang, Liguo;Wang, Shengqin;Li, Wei
通讯作者：
Li, Wei
影响因子：
2.2
作者：
Enninga EA;Nevala WK;Holtan SG;Leontovich AA;Markovic SN
通讯作者：
Markovic SN