小擎子 (2022-04-30 21:50):
#paper doi: 10.1126/science.aan4236 Nature, 2017, Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients。发现肠道微生物组可以调节黑色素瘤患者对检查点免疫疗法的反应。患者分为有应答组（R）和无应答组（NR），R组的特点是肠道微生物组有高多样性和丰度的Ruminococcaceae（瘤胃球菌科）/Faecalibacterium（粪杆菌），而NR组的肠道微生物有低多样性和高相对丰度的Bacteroidales（拟杆菌）。通过小鼠模型发现，肠道微生物组通过调节免疫细胞浸润影响了抗肿瘤免疫应答。
Science (New York, N.Y.), 2018-01-05. DOI: 10.1126/science.aan4236 PMID: 29097493 PMCID:PMC5827966
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
V Gopalakrishnan, C N Spencer, L Nezi, A Reuben, M C Andrews, T V Karpinets, P A Prieto, D Vicente, K Hoffman, S C Wei, ... >>>
V Gopalakrishnan, C N Spencer, L Nezi, A Reuben, M C Andrews, T V Karpinets, P A Prieto, D Vicente, K Hoffman, S C Wei, A P Cogdill, L Zhao, C W Hudgens, D S Hutchinson, T Manzo, M Petaccia de Macedo, T Cotechini, T Kumar, W S Chen, S M Reddy, R Szczepaniak Sloane, J Galloway-Pena, H Jiang, P L Chen, E J Shpall, K Rezvani, A M Alousi, R F Chemaly, S Shelburne, L M Vence, P C Okhuysen, V B Jensen, A G Swennes, F McAllister, E Marcelo Riquelme Sanchez, Y Zhang, E Le Chatelier, L Zitvogel, N Pons, J L Austin-Breneman, L E Haydu, E M Burton, J M Gardner, E Sirmans, J Hu, A J Lazar, T Tsujikawa, A Diab, H Tawbi, I C Glitza, W J Hwu, S P Patel, S E Woodman, R N Amaria, M A Davies, J E Gershenwald, P Hwu, J E Lee, J Zhang, L M Coussens, Z A Cooper, P A Futreal, C R Daniel, N J Ajami, J F Petrosino, M T Tetzlaff, P Sharma, J P Allison, R R Jenq, J A Wargo <<<
Abstract:
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy ( = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples ( = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity ( < 0.01) and relative abundance of bacteria of the Ruminococcaceae family ( < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.
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