决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Refining the relationship between gut microbiota and common hematologic malignancies: insights from a bidirectional Mendelian randomization study.
我们的研究为肠道菌群与血液系统恶性肿瘤之间的因果关系提供了新证据,为这些肿瘤的预防和治疗提供了新的见解和途径。
肠道微生物群与血液系统恶性肿瘤之间的关系已引起广泛关注。随着研究的进展,越来越清楚的是,肠道微生物群的组成可能影响血液系统恶性肿瘤的发生和进展。然而,我们对这种关联的理解仍然有限。
在我们的研究中,我们根据门、纲、目、科和属水平的信息将肠道微生物群分为五组。随后,我们从IEU Open GWAS项目中获取了与常见血液系统恶性肿瘤相关的数据。然后,我们采用双向孟德尔随机化(MR)方法来确定肠道微生物群与血液系统恶性肿瘤之间是否存在因果关系。此外,我们进行了双向MR分析以确定这种因果关系的方向性。
通过正向和反向MR分析,我们发现淋巴白血病的风险与门Cyanobacteria、目Methanobacteriales、纲Methanobacteria、科Peptococcaceae、科Methanobacteriaceae以及属Lachnospiraceae UCG010、Methanobrevibacter、Eubacterium brachy group和Butyrivibrio的丰度显著相关。髓系白血病的风险与门Actinobacteria、门Firmicutes、目Bifidobacteriales、目Clostridiales、纲Actinobacteria、纲Gammaproteobacteria、纲Clostridia、科Bifidobacteriaceae以及属Fusicatenibacter、Eubacterium hallii group、Blautia、Collinsella、Ruminococcus gauvreauii group和Bifidobacterium的丰度显著相关。霍奇金淋巴瘤的风险与科Clostridiales vadinBB60 group、属Peptococcus和属Ruminococcaceae UCG010的丰度显著相关。恶性浆细胞肿瘤的风险与属Romboutsia和Eubacterium rectale group的丰度显著相关。弥漫性大B细胞淋巴瘤的风险与属Erysipelatoclostridium和Eubacterium coprostanoligenes group的丰度显著相关。成熟T/NK细胞淋巴瘤的风险与门Verrucomicrobia、属Ruminococcaceae UCG013、属Lachnoclostridium和属Eubacterium rectale group的丰度显著相关。最后,骨髓增殖性肿瘤的风险与属Coprococcus 3和Eubacterium hallii group的丰度显著相关。
BACKGROUND: The relationship between gut microbiota and hematologic malignancies has attracted considerable attention. As research progresses, it has become increasingly clear that the composition of gut microbiota may influence the onset and progression of hematologic malignancies. However, our understanding of this association remains limited. METHODS: In our study, we classified gut microbiota into five groups based on information at the phylum, class, order, family, and genus levels. Subsequently, we obtained data related to common hematologic malignancies from the IEU Open GWAS project. We then employed a bidirectional Mendelian Randomization (MR) approach to determine whether there is a causal relationship between gut microbiota and hematologic malignancies. Additionally, we conducted bidirectional MR analyses to ascertain the directionality of this causal relationship. RESULTS: Through forward and reverse MR analyses, we found the risk of lymphoid leukemia was significantly associated with the abundance of phylum Cyanobacteria, order Methanobacteriales, class Methanobacteria, family Peptococcaceae, family Methanobacteriaceae, and genera Lachnospiraceae UCG010, Methanobrevibacter, Eubacterium brachy group, and Butyrivibrio. The risk of myeloid leukemia was significantly associated with the abundance of phylum Actinobacteria, phylum Firmicutes, order Bifidobacteriales, order Clostridiales, class Actinobacteria, class Gammaproteobacteria, class Clostridia, family Bifidobacteriaceae, and genera Fusicatenibacter, Eubacterium hallii group, Blautia, Collinsella, Ruminococcus gauvreauii group, and Bifidobacterium. The risk of Hodgkin lymphoma was significantly associated with the abundance of family Clostridiales vadinBB60 group, genus Peptococcus, and genus Ruminococcaceae UCG010. The risk of malignant plasma cell tumor was significantly associated with the abundance of genera Romboutsia and Eubacterium rectale group. The risk of diffuse large B-cell lymphoma was significantly associated with the abundance of genera Erysipelatoclostridium and Eubacterium coprostanoligenes group. The risk of mature T/NK cell lymphomas was significantly associated with the abundance of phylum Verrucomicrobia, genus Ruminococcaceae UCG013, genus Lachnoclostridium, and genus Eubacterium rectale group. Lastly, the risk of myeloproliferative neoplasms was significantly associated with the abundance of genus Coprococcus 3 and Eubacterium hallii group. CONCLUSION: Our study provided new evidence for the causal relationship between gut microbiota and hematologic malignancies, offering novel insights and approaches for the prevention and treatment of these tumors.
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