Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.
复制标题
DOI：
10.1371/journal.pone.0254125
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Selvaraj P
中科院分区：
文献类型：
--
作者：
Huang L;Bommireddy R;Munoz LE;Guin RN;Wei C;Ruggieri A;Menon AP;Li X;Shanmugam M;Owonikoko TK;Ramalingam SS;Selvaraj P
基于荧光和生物发光的成像技术已经成为可视化肿瘤进展以及研究药物和免疫疗法对癌症动物模型中肿瘤免疫微环境的影响的重要工具。然而，外源蛋白的转基因表达可以在具有免疫活性的同源肿瘤移植模型中诱导免疫应答，并增强实验药物的功效。在这项研究中，我们表明，刘易斯肺癌（LL/2）肿瘤的生长速度降低后，转导的tdTomato和荧光素酶（tdTomato/Luc）相比，亲本细胞系。LL/2细胞的tdTomato/Luc表达通过增加肿瘤浸润淋巴细胞（TIL）同时抑制肿瘤诱导的髓源性抑制细胞（MDSC）来改变肿瘤微环境。有趣的是，tdTomato/Luc表达没有改变LL/2肿瘤对抗PD-1和抗CTLA-4抗体的应答。这些结果表明，使用tdTomato/Luc-transduced癌细胞在免疫活性小鼠中进行研究可能会导致细胞外tdTomato/Luc-induced肿瘤生长和肿瘤免疫微环境的改变，在免疫活性动物模型中评估抗癌药物和疫苗的疗效时需要考虑这些改变。
Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immune responses in immunocompetent syngeneic tumor transplant models and augment the efficacy of experimental drugs. In this study, we show that the growth rate of Lewis lung carcinoma (LL/2) tumors was reduced after transduction of tdTomato and luciferase (tdTomato/Luc) compared to the parental cell line. tdTomato/Luc expression by LL/2 cells altered the tumor microenvironment by increasing tumor-infiltrating lymphocytes (TILs) while inhibiting tumor-induced myeloid-derived suppressor cells (MDSCs). Interestingly, tdTomato/Luc expression did not alter the response of LL/2 tumors to anti-PD-1 and anti-CTLA-4 antibodies. These results suggest that the use of tdTomato/Luc-transduced cancer cells to conduct studies in immune competent mice may lead to cell-extrinsic tdTomato/Luc-induced alterations in tumor growth and tumor immune microenvironment that need to be taken into consideration when evaluating the efficacy of anti-cancer drugs and vaccines in immunocompetent animal models.
登录
查看更多内容
影响因子：
4.8
作者：
Ansari, Amir Mehdi;Ahmed, A. Karim;Matsangos, Aerielle E.;Lay, Frank;Born, Louis J.;Marti, Guy;Harmon, John W.;Sun, Zhaoli
通讯作者：
Sun, Zhaoli
影响因子：
3.7
作者：
Pei, Yanlong;Hodgins, Douglas C.;Yoo, Dongwan
通讯作者：
Yoo, Dongwan
影响因子：
11.4
作者：
Kalyanaraman B;Zielonka J
通讯作者：
Zielonka J
影响因子：
9.7
作者：
BERTRAM, JS;JANIK, P
通讯作者：
JANIK, P
影响因子：
2.7
作者：
Burgos, JS;Rosol, M;Laug, WE
通讯作者：
Laug, WE