RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
探索肿瘤微环境在铂耐药卵巢癌中的临床价值
英文原题：Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.
查看英文原题
Exploring the clinical value of tumor microenvironment in platinum-resistant ovarian cancer.
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中文摘要
上皮性卵巢癌（OvCa）中的铂类耐药正以惊人的速度上升，化疗耐药的高级别浆液性卵巢癌（HGSC）在所有患者中约有75%出现复发。此外，HGSC的五年生存率极低，FIGO III期和IV期分别为39%和17%。本文综述了HGSC细胞与独特的腹膜肿瘤微环境（TME）中细胞及非细胞组分之间的关键细胞相互作用。我们重点阐述了细胞外基质（ECM）、腹水以及间皮细胞、肿瘤相关巨噬细胞、中性粒细胞、脂肪细胞和成纤维细胞在铂类耐药中的作用。此外，我们强调了其他免疫细胞参与者在赋予耐药性中的重要性，包括NK 细胞、髓源性抑制细胞（MDSCs）和调节性T细胞。我们展示了关键铂类耐药标志物的临床相关性及其与OvCa中主要失调通路的相关性。同时，我们讨论了免疫疗法在使铂类耐药患者对铂类药物重新敏感方面的效果。通过对HGSC中铂类耐药的详细分析，我们希望推动针对这一侵袭性疾病更有效治疗方案的开发。
展开英文摘要原文
Platinum resistance in epithelial ovarian cancer (OvCa) is rising at an alarming rate, with recurrence of chemo-resistant high grade serous OvCa (HGSC) in roughly 75 % of all patients.
Additionally, HGSC has an abysmal five-year survival rate, standing at 39 % and 17 % for FIGO stages III and IV, respectively.
Herein we review the crucial cellular interactions between HGSC cells and the cellular and non-cellular components of the unique peritoneal tumor microenvironment (TME).
We highlight the role of the extracellular matrix (ECM), ascitic fluid as well as the mesothelial cells, tumor associated macrophages, neutrophils, adipocytes and fibroblasts in platinum-resistance.
Moreover, we underscore the importance of other immune-cell players in conferring resistance, including natural killer cells, myeloid-derived suppressive cells (MDSCs) and T-regulatory cells.
We show the clinical relevance of the key platinum-resistant markers and their correlation with the major pathways perturbed in OvCa. In parallel, we discuss the effect of immunotherapies in re-sensitizing platinum-resistant patients to platinum-based drugs. Through detailed analysis of platinum-resistance in HGSC, we hope to advance the development of more effective therapy options for this aggressive disease.
论文信息
- 作者
- Ghoneum A、Almousa S、Warren B、Abdulfattah AY、Shu J、Abouelfadl H、Gonzalez D、Livingston C
- 第一作者单位
- Departments of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC, 27157, USA.United States
- 通讯作者单位
- Departments of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC, 27157, USA; Departments of Urology, Wake Forest University School of Medicine, Winston Salem, NC, 27157, USA; Comprehensive Cancer Center, Winston Salem, NC, 27157, USA. Electronic address: nsaid@wakehealth.edu.United States
- 文献类型
- 美国 NIH 资助研究 · 综述
- 期刊
- Seminars in cancer biology2021 Dec
- 原文标识
- PubMed 33476723 · DOI 10.1016/j.semcancer.2020.12.024
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