Black raspberry extract inhibits regulatory T-cell activity in a murine model of head and neck squamous cell carcinoma chemoprevention.
Black raspberry extract inhibits regulatory T-cell activity in a murine model of head and neck squamous cell carcinoma chemoprevention.
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DOI：
10.3389/fimmu.2022.932742
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发表时间：
2022
影响因子：
7.3
通讯作者：
Oghumu, Steve
中科院分区：
文献类型：
--
作者：
Ryan, Nathan M.;Lamenza, Felipe F.;Upadhaya, Puja;Pracha, Hasan;Springer, Anna;Swingler, Michael;Siddiqui, Arham;Oghumu, Steve
关键词：
头颈部鳞状细胞癌（HNSCC）是全球诊断最多的恶性肿瘤之一，5年生存率约为40%至50%。目前的治疗方法仅限于高侵入性手术、侵袭性放疗和化疗。最近的报道表明，黑树莓在抑制包括HNSCCs在内的各种癌症的进展方面具有潜在的植物化学特性。然而，黑树莓提取物对HNSCC期间肿瘤微环境免疫细胞，特别是调节性T细胞的影响尚未被研究。我们使用4-硝基喹啉-1-氧化物（4NQO）化学诱导HNSCC癌变的小鼠模型来确定这些影响。C57BL/6小鼠用4NQO喂养16周，用常规水喂养8周。4 nqo暴露小鼠分别饲喂AIN-76A对照小鼠饲粮或AIN76饲粮中添加黑覆盆子提取物。在晚期牺牲时，在肿瘤微环境、引流淋巴结和脾脏中分析肿瘤负荷和免疫细胞募集和活性。与提供AIN-76A对照日粮的小鼠相比，饲喂BRB提取物补充日粮的小鼠肿瘤负荷降低。黑树莓提取物不影响脾脏和肿瘤引流淋巴结的总体t细胞群以及Th1、Th2或Th17分化。然而，膳食中的黑树莓提取物抑制了调节性t细胞向HNSCC肿瘤部位的募集。这与肿瘤微环境中细胞毒性免疫反应的增加有关，其特征是在BRB提取物介导的HNSCC化学预防过程中CD8+ T细胞增加和颗粒酶B产生增强。有趣的是，这种增强的CD8+ t细胞抗肿瘤反应局限于肿瘤部位，而不是脾脏和引流淋巴结。此外，我们发现在黑树莓致癌物诱导小鼠的引流淋巴结中，髓系细胞群的PD-L1表达水平降低。综上所述，我们的研究结果表明，在HNSCC化学预防过程中，黑树莓提取物抑制调节性t细胞募集并促进肿瘤部位的细胞毒性CD8 t细胞活性。这些结果证明了黑树莓提取物的免疫调节潜力，并支持使用黑树莓衍生的植物化学物质作为HNSCC化学预防和治疗的补充方法。
Head and neck squamous cell carcinomas (HNSCC) are one of the most diagnosed malignancies globally, with a 5-year survival rate of approximately 40% to 50%. Current therapies are limited to highly invasive surgery, aggressive radiation, and chemotherapies. Recent reports have demonstrated the potential phytochemical properties of black raspberries in inhibiting the progression of various cancers including HNSCCs. However, the effects of black raspberry extracts on immune cells of the tumor microenvironment, specifically regulatory T cells during HNSCC, have not been investigated. We used a mouse model of 4-nitroquinoline-1-oxide (4NQO) chemically induced HNSCC carcinogenesis to determine these effects. C57BL/6 mice were exposed to 4NQO for 16 weeks and regular water for 8 weeks. 4NQO-exposed mice were fed the AIN-76A control mouse diet or the AIN76 diet supplemented with black raspberry extract. At terminal sacrifice, tumor burdens and immune cell recruitment and activity were analyzed in the tumor microenvironment, draining lymph nodes, and spleens. Mice fed the BRB extract-supplemented diet displayed decreased tumor burden compared to mice provided the AIN-76A control diet. Black raspberry extract administration did not affect overall T-cell populations as well as Th1, Th2, or Th17 differentiation in spleens and tumor draining lymph nodes. However, dietary black raspberry extract administration inhibited regulatory T-cell recruitment to HNSCC tumor sites. This was associated with an increased cytotoxic immune response in the tumor microenvironment characterized by increased CD8+ T cells and enhanced Granzyme B production during BRB extract-mediated HNSCC chemoprevention. Interestingly, this enhanced CD8+ T-cell antitumoral response was localized at the tumor sites but not at spleens and draining lymph nodes. Furthermore, we found decreased levels of PD-L1 expression by myeloid populations in draining lymph nodes of black raspberry-administered carcinogen-induced mice. Taken together, our findings demonstrate that black raspberry extract inhibits regulatory T-cell recruitment and promotes cytotoxic CD8 T-cell activity at tumor sites during HNSCC chemoprevention. These results demonstrate the immunomodulatory potential of black raspberry extracts and support the use of black raspberry-derived phytochemicals as a complementary approach to HNSCC chemoprevention and treatment.
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影响因子：
1.7
作者：
Kresty LA;Mallery SR;Stoner GD
通讯作者：
Stoner GD
影响因子：
10.9
作者：
Nishikawa H;Koyama S
通讯作者：
Koyama S
影响因子：
5.8
作者：
Mace, Thomas A.;King, Samantha A.;Ameen, Zeenath;Elnaggar, Omar;Young, Gregory;Riedl, Kenneth M.;Schwartz, Steven J.;Clinton, Steven K.;Knobloch, Thomas J.;Weghorst, Christopher M.;Lesinski, Gregory B.
通讯作者：
Lesinski, Gregory B.
DOI：
10.1002/hed.2880160506
发表时间：
1994-09-01
影响因子：
2.9
作者：
HAWKINS, BL;HENIFORD, BW;HENDLER, FJ
通讯作者：
HENDLER, FJ
影响因子：
6.2
作者：
Liu SC;Wu YC;Huang CM;Hsieh MS;Huang TY;Huang CS;Hsu TN;Huang MS;Lee WH;Yeh CT;Lin CS
通讯作者：
Lin CS