帕博西尼通过调节磷酸甘油脱氢酶刺激三阴性乳腺癌的CD8+ T细胞反应。

IF 1.8 4区 医学 Q3 ONCOLOGY
Yuanyuan Sun, Yaqing Li, Yunwei Han, Chenying Liu, Yuanming Song, Guangshen Gao
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引用次数: 0

摘要

CDK4/6抑制剂被用于治疗乳腺癌。本研究的目的是探讨帕博西尼(palbociclib, PALB)治疗三阴性乳腺癌的效果。一项体内试验被用来确定PALB对乳腺癌的影响。免疫组化检测基因表达。采用逆转录-定量PCR检测mRNA水平。western blot检测蛋白表达。流式细胞术检测CD8+ T细胞亚群扩增情况。我们发现PALB治疗促进了CD8+ T细胞的持久性,表现为干细胞样CD8+ T细胞和效应T细胞的维持。此外,PALB下调了PHGDH,高水平的PHGDH预示着乳腺癌患者预后不良。此外,过表达PHGDH可拮抗PALB的作用,抑制CD8+ T细胞的持久性。此外,PALB增强了抗pd1免疫治疗的效果,抑制了乳腺癌的肿瘤生长。综上所述,PALB通过下调PHGDH促进CD8+记忆前体在乳腺癌中的维持。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Palbociclib stimulates CD8+ T cell response in triple-negative breast cancer via regulating phosphoglycerate dehydrogenase.

CDK4/6 inhibitors are applied for the treatment of breast cancer. The purpose of this study was to explore the effects of palbociclib (PALB) on triple-negative breast cancer. An in vivo assay was applied to determine the effects of PALB on breast cancer. Gene expression was detected using immunohistochemistry. mRNA levels were detected using reverse transcription-quantitative PCR. Protein expression was detected using western blot. The expansion of CD8+ T cell subsets was detected using flow cytometry. We found that PALB treatment promoted the persistence of CD8+ T cells, manifested by the maintenance of stem-like CD8+ T cells and effector T cells. Moreover, PALB downregulated PHGDH, high levels of which predicted poor prognosis of breast cancer patients. Moreover, overexpression of PHGDH antagonized the effects of PALB and suppressed the persistence of CD8+ T cells. Additionally, PALB enhanced the effects of anti-PD1 immunotherapy and suppressed the tumor growth of breast cancer. In summary, PALB promoted the maintenance of CD8+ memory precursors in breast cancer via downregulating PHGDH.

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来源期刊
Anti-Cancer Drugs
Anti-Cancer Drugs 医学-药学
CiteScore
3.80
自引率
0.00%
发文量
244
审稿时长
3 months
期刊介绍: Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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