糖酸突变酶1通过诱导免疫抑制性M2巨细胞促进乳腺癌的进展
Dong Zhang1,2,3,4,5,6,7, Min Wang1,2,3,4,5,6, Shiya Ma1,2,3,4,5,6
1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Cancer gene therapy
|May 15, 2024
概括
研究人员发现,在乳腺癌 (BC) 中抑制糖酸突变酶1 (PGAM1) 通过影响巨细胞来减少免疫抑制瘤微环境 (TME). 向PGAM1和CCL2/CCR2轴为BC提供了一个新的组合治疗策略.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 瘤微环境 (TME) 对瘤进展和抗癌疗法具有至关重要的作用.
- 糖酸突变酶1 (PGAM1) 是癌症中的关键代谢酶,但其在TME调节中的作用尚不清楚.
研究的目的:
- 研究PGAM1在塑造乳腺癌 (BC) 中免疫抑制性TME中的作用.
- 探索PGAM1对巨细胞行为和招募的影响.
- 评估针对PGAM1与其他途径结合的治疗潜力.
主要方法:
- 研究了PGAM1抑制对BC细胞中巨细胞极化,迁移和细胞因子产生的影响.
- 通过JAK-STAT途径分析了CCL2表达和巨细胞招募的调节.
- 研究了CCL2/CCR2轴在PGAM1-介导免疫抑制和PD-1表达中的作用.
- 在体内评估了联合PGAM1和CCL2/CCR2轴向的有效性.
- 在临床BC样本中,与巨细胞透相关的PGAM1和CCL2水平.
主要成果:
- 抑制PGAM1降低了巨细胞中的M2极化,迁移和IL-10产生.
- PGAM1通过CCL2表达调节巨细胞的招募,从而激活JAK-STAT通路.
- CCL2/CCR2轴通过调节巨细胞上的PD-1表达方式,参与PGAM1介导的免疫抑制.
- 对PGAM1和CCL2/CCR2轴的联合向在体内显著降低了瘤生长.
- 临床BC组织显示PGAM1,CCL2和巨细胞透之间存在正相关性.
结论:
- 通过影响巨细胞功能和招募,PGAM1在乳腺癌中积极诱导免疫抑制性TME.
- 针对PGAM1,特别是与CCL2/CCR2轴相结合,为乳腺癌提供了一个有前途的治疗策略.
- 这项研究为PGAM1在癌症免疫抑制中的作用提供了新的见解,并为新型组合疗法提供了基础.
相关概念视频
03:03mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
02:23Abnormal Proliferation
4.5K
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...
4.5K
02:07Tumor Progression
6.3K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.3K
02:53Adaptive Mechanisms in Cancer Cells
5.7K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
02:17The Tumor Microenvironment
6.6K
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...
6.6K