HMGA2将形态演变和微环境动态与清细胞细胞癌的系统治疗反应联系在一起
Takahiro Nakamoto1,2, Takashi Yoshida3,4, Chisato Ohe1,5
1Department of Urology and Andrology, Kansai Medical University, Hirakata, Osaka, Japan.
Journal for immunotherapy of cancer
|November 25, 2025
概括
高流动性组AT-hook 2 (HMGA2) 表达与侵略性的清细胞细胞癌 (ccRCC) 形态相关,并预测免疫检查点抑制剂组合治疗的反应. HMGA2影响瘤免疫微环境,表明其作为治疗标记物的潜力.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 免疫学 免疫学 免疫学
背景情况:
- 清细胞细胞癌 (ccRCC) 显示出显著的异质性,影响治疗结果.
- 高流动性组AT-hook 2 (HMGA2) 在ccRCC进展中的作用及其临床相关性尚未确定.
研究的目的:
- 研究HMGA2在ccRCC形态演变中的作用及其对瘤免疫微环境的影响.
- 评估HMGA2表达与全身治疗反应相关的临床意义.
主要方法:
- 在ccRCC样本上使用空间转录学 (ST) 和单细胞RNA测序 (scRNA-seq).
- 免疫组织化学 (IHC) 和大量RNA测序分析了分子和临床特征.
- 多重免疫组织化学 (mIHC) 评估了免疫细胞的分布和相互作用.
主要成果:
- HMGA2的表达与激进的ccRCC形态和细胞循环和炎症等途径有关.
- 高HMGA2瘤的无进展生存率较差,但对组合免疫检查点抑制剂 (Combo-ICI) 的反应更好.
- 高HMGA2瘤的特征是富含的 CD8+ T细胞 (Tpex),通过ICAM-1与树突细胞 (cDC) 相互作用,特别是在组合ICI反应者中.
结论:
- 动态HMGA2表达驱动ccRCC形态变化和免疫调节.
- 在ccRCC中,HMGA2可以作为系统治疗反应的预测生物标志物.
- 需要进一步的实验研究来证实这些机制.
更多相关视频
05:36Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
9.4K
06:38A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
14.1K
相关概念视频
The Tumor Microenvironment
7.6K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.6K
Mitogens and the Cell Cycle
7.7K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.7K
mTOR Signaling and Cancer Progression
4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
4.6K
Abnormal Proliferation
5.1K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
Metastasis
6.3K
Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
6.3K
