Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas

被引:52
作者
Huang, Yu [1 ]
Zhu, Ning [2 ]
Zheng, Xing [2 ]
Liu, Yanhong [2 ]
Lu, Haopeng [2 ]
Yin, Xiaochen [2 ]
Hao, Huaijie [2 ]
Tan, Yan [2 ]
Wang, Dongjie [3 ]
Hu, Han [2 ]
Liang, Yong [2 ]
Li, Xinxing [4 ]
Hu, Zhiqian [4 ,5 ]
Yin, Yiming [2 ]
机构
[1] 903 Hosp Peoples Liberat Army Joint Logist Suppor, Dept Gen Surg, Hangzhou, Peoples R China
[2] Shenzhen Xbiome Biotech Co Ltd, Dept Res & Dev, Shenzhen, Peoples R China
[3] Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Inst Synthet Biol, Shenzhen, Peoples R China
[4] Tongji Univ, Tongji Hosp, Sch Med, Dept Gen Surg, Shanghai, Peoples R China
[5] Second Mil Med Univ, Changzheng Hosp, Dept Gen Surg, Shanghai, Peoples R China
关键词
PDAC (pancreatic ductal adenocarcinoma); intratumor microbiome; 16S rRNA (amplicon sequencing); Megasphaera; immune stimulatory; TUMOR MICROBIOME; CANCER; BUTYRATE;
D O I
10.3389/fimmu.2022.785422
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Human tumors harbor a plethora of microbiota. It has been shown that the composition and diversity of intratumor microbiome are significantly associated with the survival of patients with pancreatic ductal adenocarcinoma (PDAC). However, the association in Chinese patients as well as the effect of different microorganisms on inhibiting tumor growth are unclear. In this study, we collected tumor samples resected from long-term and short-term PDAC survivors and performed 16S rRNA amplicon sequencing. We found that the microbiome in samples with different survival time were significantly different, and the differential bacterial composition was associated with the metabolic pathways in the tumor microenvironment. Furthermore, administration of Megasphaera, one of the differential bacteria, induced a better tumor growth inhibition effect when combined with the immune checkpoint inhibitor anti-programmed cell death-1 (anti-PD-1) treatment in mice bearing 4T1 tumor. These results indicate that specific intratumor microbiome can enhance the anti-tumor effect in the host, laying a foundation for further clarifying the underlying detailed mechanism.
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页数:12
相关论文
共 54 条
[1]   Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer [J].
Balachandran, Vinod P. ;
Luksza, Marta ;
Zhao, Julia N. ;
Makarov, Vladimir ;
Moral, John Alec ;
Remark, Romain ;
Herbst, Brian ;
Askan, Gokce ;
Bhanot, Umesh ;
Senbabaoglu, Yasin ;
Wells, Daniel K. ;
Cary, Charles Ian Ormsby ;
Grbovic-Huezo, Olivera ;
Attiyeh, Marc ;
Medina, Benjamin ;
Zhang, Jennifer ;
Loo, Jennifer ;
Saglimbeni, Joseph ;
Abu-Akeel, Mohsen ;
Zappasodi, Roberta ;
Riaz, Nadeem ;
Smoragiewicz, Martin ;
Kelley, Z. Larkin ;
Basturk, Olca ;
Goenen, Mithat ;
Levine, Arnold J. ;
Allen, Peter J. ;
Fearon, Douglas T. ;
Merad, Miriam ;
Gnjatic, Sacha ;
Iacobuzio-Donahue, Christine A. ;
Wolchok, Jedd D. ;
DeMatteo, Ronald P. ;
Chan, Timothy A. ;
Greenbaum, Benjamin D. ;
Merghoub, Taha ;
Leach, Steven D. .
NATURE, 2017, 551 (7681) :512-+
[2]   Controlling the false discovery rate in behavior genetics research [J].
Benjamini, Y ;
Drai, D ;
Elmer, G ;
Kafkafi, N ;
Golani, I .
BEHAVIOURAL BRAIN RESEARCH, 2001, 125 (1-2) :279-284
[3]   The Role of the Microbiome in Cancer Development and Therapy [J].
Bhatt, Aadra P. ;
Redinbo, Matthew R. ;
Bultman, Scott J. .
CA-A CANCER JOURNAL FOR CLINICIANS, 2017, 67 (04) :327-344
[4]   Association of Fusobacterium nucleatum with Specific T-cell Subsets in the Colorectal Carcinoma Microenvironment [J].
Borowsky, Jennifer ;
Haruki, Koichiro ;
Lau, Mai Chan ;
Costa, Andressa Dias ;
Vayrynen, Juha P. ;
Ugai, Tomotaka ;
Arima, Kota ;
da Silva, Annacarolina ;
Felt, Kristen D. ;
Zhao, Melissa ;
Gurjao, Carino ;
Twombly, Tyler S. ;
Fujiyoshi, Kenji ;
Vayrynen, Sara A. ;
Hamada, Tsuyoshi ;
Mima, Kosuke ;
Bullman, Susan ;
Harrison, Tabitha A. ;
Phipps, Amanda, I ;
Peters, Ulrike ;
Ng, Kimmie ;
Meyerhardt, Jeffrey A. ;
Song, Mingyang ;
Giovannucci, Edward L. ;
Wu, Kana ;
Zhang, Xuehong ;
Freeman, Gordon J. ;
Huttenhower, Curtis ;
Garrett, Wendy S. ;
Chan, Andrew T. ;
Leggett, Barbara A. ;
Whitehall, Vicki L. J. ;
Walker, Neal ;
Brown, Ian ;
Bettington, Mark ;
Nishihara, Reiko ;
Fuchs, Charles S. ;
Lennerz, Jochen K. ;
Giannakis, Marios ;
Nowak, Jonathan A. ;
Ogino, Shuji .
CLINICAL CANCER RESEARCH, 2021, 27 (10) :2816-2826
[5]  
Callahan BJ, 2016, NAT METHODS, V13, P581, DOI [10.1038/NMETH.3869, 10.1038/nmeth.3869]
[6]   Metabolic modulation of tumours with engineered bacteria for immunotherapy [J].
Canale, Fernando P. ;
Basso, Camilla ;
Antonini, Gaia ;
Perotti, Michela ;
Li, Ning ;
Sokolovska, Anna ;
Neumann, Julia ;
James, Michael J. ;
Geiger, Stefania ;
Jin, Wenjie ;
Theurillat, Jean-Philippe ;
West, Kip A. ;
Leventhal, Daniel S. ;
Lora, Jose M. ;
Sallusto, Federica ;
Geiger, Roger .
NATURE, 2021, 598 (7882) :662-+
[7]   Biofilm formation of Clostridium perfringens and its exposure to low-dose antimicrobials [J].
Charlebois, Audrey ;
Jacques, Mario ;
Archambault, Marie .
FRONTIERS IN MICROBIOLOGY, 2014, 5
[8]   An omnibus test for differential distribution analysis of microbiome sequencing data [J].
Chen, Jun ;
King, Emily ;
Deek, Rebecca ;
Wei, Zhi ;
Yu, Yue ;
Grill, Diane ;
Ballman, Karla .
BIOINFORMATICS, 2018, 34 (04) :643-651
[9]   Recent advances in immunotherapy for pancreatic cancer [J].
Chi, Jeffrey ;
Patel, Rajvi ;
Rehman, Hasan ;
Goyal, Shreya ;
Saif, Muhammad Wasif .
JOURNAL OF CANCER METASTASIS AND TREATMENT, 2020, 6
[10]   Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-upaEuro [J].
Ducreux, M. ;
Cuhna, A. Sa. ;
Caramella, C. ;
Hollebecque, A. ;
Burtin, P. ;
Goere, D. ;
Seufferlein, T. ;
Haustermans, K. ;
Van Laethem, J. L. ;
Conroy, T. ;
Arnold, D. .
ANNALS OF ONCOLOGY, 2015, 26 :V56-V68