CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Gut Microbiota Dysbiosis and Dietary Interventions in Non-Hodgkin B-Cell Lymphomas: Implications for Treatment Response.
Gut Microbiota Dysbiosis and Dietary Interventions in Non-Hodgkin B-Cell Lymphomas: Implications for Treatment Response.
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非霍奇金B细胞淋巴瘤是一组异质性淋巴系统恶性肿瘤,在生物学行为、临床表现和治疗应答方面各不相同。化学免疫治疗仍是其治疗基石,但越来越多证据表明,肠道微生物群是调节淋巴瘤发生和治疗疗效的重要因素。新诊断患者中也观察到肠道菌群失调,其特征包括微生物多样性下降和菌群分类组成向致病性偏移,并非仅由治疗引起。这种失衡会破坏黏膜屏障、促进全身炎症并改变免疫应答,进而影响疗效和毒性。抗生素暴露,尤其是广谱抗生素,会加重菌群失调,并与免疫化疗及CAR-T 疗效较差相关。相反,某些共生菌,如普拉梭菌和约氏乳杆菌,可能通过维持黏膜稳态、促进抗肿瘤免疫发挥保护作用。目前正在研究多种针对性干预措施,以恢复菌群稳态并改善临床结局,包括合理管理抗生素、使用益生元和益生菌、饮食调节及粪菌移植。初步临床试验提示,基线微生物组组成与治疗应答密切相关。仍需开展机制研究和随机试验,以明确微生物组在非霍奇金B细胞淋巴瘤病理生理中的因果作用,并开发可作为标准治疗辅助措施的个体化菌群调节策略。
Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles.
Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity.
Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response.
Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment.
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