在癌症中,免疫逃脱的进化轨迹跨越癌症
Wenjie Chen1, Toby Baker2,3,4, Zhihui Zhang2
1Department of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
bioRxiv : the preprint server for biology
|January 27, 2025
概括
癌症免疫逃脱在不同类型的癌症中演变不同,特定的遗传事件发生在瘤发育的不同阶段. 了解这些进化轨迹可以改善癌症免疫治疗策略.
科学领域:
- 在瘤学瘤学.
- 癌症基因组学 癌症基因组学
- 免疫学 免疫学 免疫学
背景情况:
- 免疫逃生是癌症进展和免疫治疗耐药性的关键因素.
- 在癌症发育过程中驱动免疫逃脱的遗传事件的时间在很大程度上是未知的.
研究的目的:
- 为了重建38种癌症类型中免疫逃脱的进化轨迹.
- 在不同癌症中识别特定的免疫调节途径及其突变时间.
主要方法:
- 功能基因组学数据与瘤进化重建的整合.
- 全基因组全癌症分析数据集的分析.
- 检查免疫调节通路的突变,包括抗原呈现,蛋白质甲基化和信号通路.
主要成果:
- 不同的癌症在免疫调节途径中表现出不同的突变模式 (例如,抗原呈现机制,蛋白质甲基化).
- 特定的途径在不同癌症类型中显示出不同的突变时间 (例如,胰腺癌晚期的氨基酸代谢,淋巴瘤晚期的TNF途径).
- 像NOD1/2信号传递和DNA结合转录因子活性等途径的突变在乳腺和卵巢腺癌中发生晚期.
结论:
- 这项研究描绘了在不同类型的癌症中免疫逃脱的进化路径.
- 识别遗传事件的时间为优化癌症免疫治疗方法提供了洞察力.
相关概念视频
Tumor Immunotherapy
466
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.
466
Treatment Resistant Cancers
3.2K
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...
3.2K
Tumor Progression
6.2K
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...
6.2K
Cytotoxic T Cells-mediated Immune Response
835
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
835
Metastasis
5.5K
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...
5.5K
Cancers Originate from Somatic Mutations in a Single Cell
11.5K
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...
11.5K


