在微卫星不稳定性高的结直肠癌中,免疫逃生机制的亚克隆积累
Yuta Kobayashi1,2, Atsushi Niida3, Satoshi Nagayama4,5
1Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, 874-0838, Japan.
British journal of cancer
|August 18, 2023
概括
在微卫星不稳定性高的结直肠癌中,内瘤异质性源于达尔文的选择,免疫逃生机制以亚克隆方式发展. 早期免疫检查点抑制剂治疗可能是有效的.
科学领域:
- 在瘤学瘤学.
- 癌症 演化 演化 癌症 演化
- 免疫基因组学是什么
背景情况:
- 在微观卫星不稳定性高 (MSI-H) 大肠直肠癌 (CRC) 中,瘤内异质性 (ITH) 尚未得到研究.
- 了解MSI-H CRC中的ITH驱动因素和免疫压力影响至关重要.
研究的目的:
- 为了研究MSI-H CRC进化中的ITH生成.
- 为了确定免疫选择性压力对ITH在MSI-H CRC中的影响.
主要方法:
- 重新分析来自246个MSI-H CRC的公开整体外因子测序数据.
- 对6个MSI-H CRC进行了多区域分析.
- 在免疫压力下的癌症进化计算模型的开发.
主要成果:
- 在抗原呈现机制 (APM) 中观察到基因组变化的丰富.
- 免疫逃生机制与HLA变化和新抗原生成有关.
- 发生了APM缺陷和驱动突变的亚克隆积累,亚克隆突变经历了选择性扫描.
- 计算模拟证实了亚克隆性免疫逃脱,并建议早期免疫检查点抑制剂 (ICI) 的有效性.
结论:
- 在MSI-HCRC中,异质免疫逃生机制是通过达尔文选择获得的.
- 这些发现为MSI-H CRC的ICI治疗策略提供了新的见解.
更多相关视频
相关概念视频
Cancer Stem Cells and Tumor Maintenance
5.0K
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...
5.0K
Adaptive Mechanisms in Cancer Cells
5.8K
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,...
5.8K
Metastasis
5.6K
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...
5.6K
Treatment Resistant Cancers
3.3K
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...
3.3K
Cancers Originate from Somatic Mutations in a Single Cell
12.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
12.0K
Mismatch Repair
4.9K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.9K


