单细胞转录组分析揭示了在结直肠癌免疫治疗期间与瘤耐药性相关的调节程序
Yan Chen1, Tao Liu1, Guangtao Min2
1The First Clinical Medical College of Lanzhou University, Lanzhou, China.
International journal of surgery (London, England)
|September 11, 2025
概括
在结直肠癌 (CRC) 中,T细胞子集驱动免疫治疗的耐药性. 转录性变化和T细胞中受损的细胞通信有助于耐药性,KLRB1成为治疗反应的有希望的生物标志物.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 基因组学就是基因组学.
背景情况:
- 大肠直肠癌 (CRC) 是全球领先的癌症.
- 免疫检查点抑制剂 (ICI) 在转移性DNA不匹配修复缺陷 (dMMR) CRC中显示出有效性.
- 在CRC中免疫疗法耐药性的机制尚不清楚.
研究的目的:
- 研究dMMRCRC中T细胞子集在免疫疗法耐药性中的作用.
- 确定药物耐药性背后的分子机制.
- 评估KLRB1作为治疗反应的潜在生物标志物.
主要方法:
- 单细胞测序用于分析细胞群和基因表达.
- 基因组丰富分析 (GSEA) 用于途径识别.
- 细胞通信分析以研究T细胞相互作用.
- 临床CRC样本上的免疫组织化学 (IHC) 检测FOS和KLRB1的表达.
主要成果:
- 包括耗尽的T细胞 (Tex),GZMK+ T,TSTR,调节性T细胞 (Treg) 和γδ_T细胞在内的T细胞子集与免疫疗法耐药性有关.
- 在耐药瘤中观察到TSTR和γδ_T细胞的转录失调以及改变的信号通路.
- 降低CD69-KLRB1通路的调节和增加FOS表达与预后不佳相关,而KLRB1表达预测了更好的结果.
结论:
- 在转移性dMMRCRC中,T细胞子集在抗PD-1疗法耐药性方面发挥着至关重要的作用.
- 转录失调和T细胞中受损的细胞通信是药物耐药性的关键机制.
- KLRB1是预测CRC患者免疫治疗反应的潜在生物标志物.
相关概念视频
Tumor Immunotherapy
1.8K
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
1.8K
Cancer-Critical Genes II: Tumor Suppressor Genes
9.4K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.4K
Treatment Resistant Cancers
3.7K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.7K
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
Cancer Stem Cells and Tumor Maintenance
5.9K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.9K
Adaptive Mechanisms in Cancer Cells
7.0K
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,...
7.0K


