在肝细胞癌中,Bifidobacterium通过JAK通路提高了抗PD-1的有效性
Ran Huo1, Quan-Guo Xu2, Yi-Qing You2
1Department of Clinical Laboratory, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China. ranhuo863@163.com.
NPJ precision oncology
|July 23, 2025
概括
肠道细菌如Bifidobacterium及其代谢物异黄油酸可能会改善肝癌免疫疗法. 这项研究发现,这些元素增强了抗瘤免疫反应,为抗肝细胞癌 (HCC) 提供了新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
背景情况:
- 肝细胞癌 (HCC) 是一个主要的全球健康问题.
- 肠道微生物组在癌症免疫力和免疫疗法的作用越来越被认可,但尚未完全理解.
- 关联肠道微生物群与HCC进展和治疗反应的机制需要阐明.
研究的目的:
- 为了研究HCC患者和健康对照 (HC) 之间的肠道微生物组成的差异.
- 探索特定肠道细菌及其代谢物对HCC生长和免疫治疗的影响.
- 阐明肠道微生物介导的抗瘤作用背后的细胞和分子机制.
主要方法:
- 使用16S rDNA测序和代谢学来分析HC患者和HC患者的肠道微生物群.
- HCC的动物模型用便微生物群移植和/或免疫疗法 (αPD-1) 进行治疗.
- 实验室试验检查了异酸盐对免疫细胞和癌细胞的影响,包括途径分析 (JAK/STAT3).
主要成果:
- 与HCC患者相比,健康对照组的Bifidobacterium水平较高,Bifidobacterium和异黄油酸之间存在正相关性.
- 与αPD-1免疫疗法相结合的HC便物与αPD-1便物相比,显示出优异的瘤减少.
- 与αPD-1一起使用Bifidobacterium或异酸盐,显著降低了瘤大小.
- 异芽酸盐增强了CD8+T细胞活性 (IFN-γ分泌) 并在体外抑制了肝癌细胞,降低了JAK/STAT3通路的调节.
- 联合治疗促进了CD8+T细胞透和IFN-γ水平,同时降低了瘤微环境中的JAK/STAT3信号传递.
结论:
- 比菲多细菌及其代谢物异芽酸盐具有与肝细胞癌相关的抗瘤特性.
- 这些发现突显了调节肠道微生物群及其代谢物的潜力,以提高HCC免疫疗法的疗效.
- 针对Bifidobacterium-isobutyrate轴提供了一个有希望的策略,以克服HCC的免疫疗法耐药性.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
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...
4.0K
The JAK-STAT Signaling Pathway
9.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.2K
Interactions Between Signaling Pathways
6.5K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.5K
TGF - β Signaling Pathway
7.7K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.7K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
235
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
235
Tumor Immunotherapy
662
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.
662


