西红花提取物调控免疫细胞,提高程序性死亡受体-1抑制剂治疗肺腺癌效果的实验研究

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中文摘要：目的:多项研究提示,西红花提取物能影响肿瘤的发展进程.本实验探究西红花提取物在肺腺癌小鼠模型中对肿瘤免疫微环境和免疫治疗的影响,为西红花提取物抗肿瘤研究提供更多基础性数据.方法:构建Lewis肺癌细胞和萤光素酶稳定结合的小鼠皮下瘤模型,观察西红花提取物对小鼠皮下瘤和肿瘤免疫微环境的影响:运用活体成像技术跟踪肿瘤生长情况;运用流式细胞技术检测小鼠CD4+、CD8+ T细胞的数量及占比;运用反转录-聚合酶链式反应技术检测程序性死亡受体配体 1、含有T细胞免疫球蛋白和黏蛋白结构域的蛋白 3(T cell immunoglobulin and mucin domain-containing protein 3,TIM3)、淋巴细胞活化基因-3(lymphocyte-activation gene-3,LAG3)、具有免疫球蛋白和ITIM结构域的T细胞免疫受体(T cell immunoreceptor with immunoglobulin and ITIM domain,TIGIT)、胸腺细胞选择相关的高迁移率族蛋白(thymocyte selection-associated high mobility group box,TOX)1、TOX2、TOX3 基因的mRNA表达情况.结果:与对照组相比,给予西红花提取物能一定程度地抑制小鼠皮下瘤的生长(P＜0.05),且小鼠CD4+、CD8+ T细胞的数量及占比均增加(P＜0.05),TIM3、LAG3、TIGIT、TOX1、TOX2、TOX3 的基因表达均上调(P＜0.05).结论:西红花提取物能提高肺腺癌免疫微环境中的CD4+、CD8+ T细胞的占比,增强免疫治疗的抗肿瘤作用,进而提高肺癌免疫治疗效果,抑制肺癌发展.

外文标题：Experimental study of saffron extracts to modulate immune cells to improve the efficacy of a programmed death-1 inhibitor in the treatment of lung adenocarcinoma

外文摘要：Objective:A number of studies have shown that saffron extracts can affect the development of tumor.This study explored the effect of saffron extract on tumor immune microenvironment and immunotherapy in a mouse model of lung adenocarcinoma so as to provide more basic data for the anti-tumor research of saffron extracts.Methods:The transplanted tumor model of Lewis lung carcinoma-luciferase in mice was established to detect the effect of saffron extracts on the transplanted tumor in vivo.At the same time,the tumor growth was tracked by in vivo imaging technique.The number and proportion of CD4+ and CD8+ T cells were determined by flow cytometry.The mRNA levels of programmed death-ligand 1,T cell immunoglobulin and mucin domain-containing protein 3(TIM3),lymphocyte-activation gene-3(LAG3),T cell immunoreceptor with immunoglobulin and ITIM domain(TIGIT),thymocyte selection-associated high mobility group box(TOX)1,TOX2 and TOX3 were detected by reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemical techniques to verify the effect of saffron extracts on the regulation of tumor immune microenvironment.Results:Compared with the control group,the administration of saffron extracts could inhibit the growth of subcutaneous tumor in mice to a certain extent,and the number and proportion of CD4+ and CD8+ T cells were increased(P<0.05),and the expression of genes encoding TIM3,LAG3,TIGIT,TOX1,TOX2 and TOX3 was up-regulated(P<0.05).Conclusion:The saffron extracts can increase the proportion of CD4+ and CD8+ T cells in tumor microenvironment,enhance the anti-tumor effect of immunotherapy,thereby improving the effect of lung cancer immunotherapy and inhibiting the development of lung cancer.

外文关键词：

saffronimmune microenvironmentlung adenocarcinomaimmunotherapy

作者：

李诗颖、李存雅、张雪、钟薏

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作者单位：

上海中医药大学附属上海市中西医结合医院肿瘤科上海 200082

上海市药材有限公司上海 200082

关键词：

西红花免疫微环境肺腺癌免疫治疗

基金：

上海市2022年度"科技创新行动计划"医学创新研究专项项目上海市虹口区第二轮"国医强优"三年行动计划(2022-2024年)中西医结合重点专科、薄弱专科建设项目上海市2021年度"科技创新行动计划"扬帆计划项目上海市2022年度"科技创新行动计划"启明星培育(扬帆专项)项目山东省乡村振兴基金会张秀兰慈善基金项目

项目编号：

22Y31920104HKGYQYXM-2022-1021YF44440022YF1444900

出版年：

2024

上海医药

上海医药行业协会

上海医药

影响因子：0.781

ISSN：1006-1533

年,卷(期)：2024.45(1)

参考文献量4