肿瘤细胞治疗研究
英文原题：Modulation of the gut microbiota engages antigen cross-presentation to enhance antitumor effects of CAR T cell immunotherapy.
多项研究已表明共生微生物对T细胞功能的影响，特别是在癌症检查点免疫治疗中。
多项研究已显示共生微生物对T细胞功能的影响，尤其是在癌症检查点免疫治疗背景下。在本研究中，我们利用多种临床前模型以及临床相关性，探讨了万古霉素诱导的肠道菌群失调如何影响嵌合抗原受体（CAR）T免疫治疗。在两种小鼠肿瘤模型，即造血性CD19+-A20淋巴瘤和CD19+-B16黑色素瘤中，与单独接受CD19导向CAR T细胞（CART-19）治疗相比，接受万古霉素联合CART-19治疗的小鼠表现出更强的肿瘤控制以及肿瘤相关抗原（TAAs）交叉呈递。将来自人类健康供体的粪便微生物移植给预处理小鼠后，重现了在未处理肠道菌群小鼠中获得的结果。最后，接受CART-19治疗并暴露于口服万古霉素的B细胞急性淋巴细胞白血病患者，与未暴露患者相比，表现出更高的CART-19峰值扩增。这些结果证实了肠道菌群对CAR T细胞治疗的作用，并提示使用万古霉素调节肠道菌群可能改善跨肿瘤类型的CAR T细胞治疗后的结局。
Several studies have shown the influence of commensal microbes on T cell function, specifically in the setting of checkpoint immunotherapy for cancer. In this study, we investigated how vancomycin-induced gut microbiota dysbiosis affects chimeric antigen receptor (CAR) T immunotherapy using multiple preclinical models as well as clinical correlates. In two murine tumor models, hematopoietic CD19 + -A20 lymphoma and CD19 + -B16 melanoma, mice receiving vancomycin in combination with CD19-directed CAR T cell (CART-19) therapy displayed increased tumor control and tumor-associated antigens (TAAs) cross-presentation compared with CART-19 alone. Fecal microbiota transplant from human healthy donors to pre-conditioned mice recapitulated the results obtained in naive gut microbiota mice. Last, B cell acute lymphoblastic leukemia patients treated with CART-19 and exposed to oral vancomycin showed higher CART-19 peak expansion compared with unexposed patients. These results substantiate the role of the gut microbiota on CAR T cell therapy and suggest that modulation of the gut microbiota using vancomycin may improve outcomes after CAR T cell therapy across tumor types.
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