Unexpected guests in the tumor microenvironment: microbiome in cancer

doi:10.1007/s13238-020-00813-8

Protein Cell

2021, Vol. 12

Issue (5) : 426-435 https://doi.org/10.1007/s13238-020-00813-8

REVIEW

Unexpected guests in the tumor microenvironment: microbiome in cancer

Abigail Wong-Rolle¹, Haohan Karen Wei², Chen Zhao¹(

), Chengcheng Jin²(

)

¹. Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, 4 Memorial Drive, Bethesda, MD 20892, USA
². Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Blvd., Philadelphia, PA 19104, USA

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Abstract

Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.

Keywords microbiome tumor lung cancer immune system tumor-associated microbiota cancer immunotherapy

Corresponding Author(s): Chen Zhao,Chengcheng Jin

Online First Date: 11 January 2021 Issue Date: 08 June 2021

Cite this article:

Abigail Wong-Rolle,Haohan Karen Wei,Chen Zhao, et al. Unexpected guests in the tumor microenvironment: microbiome in cancer[J]. Protein Cell, 2021, 12(5): 426-435.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00813-8
https://academic.hep.com.cn/pac/EN/Y2021/V12/I5/426

1	MT Abreu, RM Jr Peek (2014) Gastrointestinal malignancy and the microbiome. Gastroenterology 146:1534–1546.e1533 https://doi.org/10.1053/j.gastro.2014.01.001
2	JC Arthur, E Perez-Chanona, M Muhlbauer, S Tomkovich, JM Uronis, TJ Fan, BJ Campbell, T Abujamel, B Dogan, AB Rogerset al. (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123 https://doi.org/10.1126/science.1224820
3	B Aykut, S Pushalkar, R Chen, Q Li, R Abengozar, JI Kim, SA Shadaloey, D Wu, P Preiss, N Vermaet al. (2019) The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574:264–267 https://doi.org/10.1038/s41586-019-1608-2
4	VP Balachandran, M Łuksza, JN Zhao, V, Makarov JA Moral, R Remark, B Herbst, G, Askan U Bhanot, Y Senbabaogluet al. (2017) Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature 551:512–516 https://doi.org/10.1038/nature24462
5	S Banerjee, T Tian, Z Wei, N Shih, MD Feldman, KN Peck, AM DeMichele, JC Alwine, ES Robertson (2018) Distinct microbial signatures associated with different breast cancer types. Front Microbiol 9:951 https://doi.org/10.3389/fmicb.2018.00951
6	RP Baughman, JE Thorpe, J, Staneck M Rashkin, PT Frame (1987) Use of the protected specimen brush in patients with endotracheal or tracheostomy tubes. Chest 91:233–236 https://doi.org/10.1378/chest.91.2.233
7	Y Belkaid, TW Hand (2014) Role of the microbiota in immunity and inflammation. Cell 157:121–141 https://doi.org/10.1016/j.cell.2014.03.011
8	Y, Belkaid S Naik (2013) Compartmentalized and systemic control of tissue immunity by commensals. Nat Immunol 14:646–653 https://doi.org/10.1038/ni.2604
9	S Bullman, CS Pedamallu, E Sicinska, TE Clancy, X Zhang, D Cai, D Neuberg, K Huang, F Guevara, T Nelsonet al. (2017) Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358:1443–1448 https://doi.org/10.1126/science.aal5240
10	SJS Cameron, KE Lewis, SA Huws, MJ Hegarty, PD Lewis, JA Pachebat, LAJ Mur (2017) A pilot study using metagenomic sequencing of the sputum microbiome suggests potential bacterial biomarkers for lung cancer. PLoS ONE 12:e0177062 https://doi.org/10.1371/journal.pone.0177062
11	M Castellarin, RL Warren, JD Freeman, L Dreolini, M Krzywinski, J Strauss, R, Barnes P Watson, E Allen-Vercoe, RA Mooreet al. (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22:299–306 https://doi.org/10.1101/gr.126516.111
12	ES Charlson, K Bittinger, AR Haas, AS Fitzgerald, I Frank, A Yadav, FD Bushman, RG Collman (2011) Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med 184:957–963 https://doi.org/10.1164/rccm.201104-0655OC
13	YE Chen, H Tsao (2013) The skin microbiome: current perspectives and future challenges. J Am Acad Dermatol 69:143–155 https://doi.org/10.1016/j.jaad.2013.01.016
14	EK Costello, CL Lauber, M Hamady, N Fierer, JI Gordon, R Knight (2009) Bacterial community variation in human body habitats across space and time. Science (New York NY) 326:1694–1697 https://doi.org/10.1126/science.1177486
15	C de Martel , J Ferlay, S Franceschi, J, Vignat F, Bray D Forman, M Plummer (2012) Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol 13:607–615 https://doi.org/10.1016/S1470-2045(12)70137-7
16	CM Dejea, P Fathi, JM Craig, A Boleij, R Taddese, AL Geis, X Wu, CE DeStefano Shields, EM Hechenbleikner, DL Husoet al. (2018) Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359:592–597 https://doi.org/10.1126/science.aah3648
17	RP Dickson, JR Erb-Downward, CM Freeman, L McCloskey, JM Beck, GB Huffnagle, JL Curtis (2015) Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography. Ann Am Thorac Soc 12:821–830 https://doi.org/10.1513/AnnalsATS.201501-029OC
18	RP Dickson, JR Erb-Downward, GB Huffnagle (2013) The role of the bacterial microbiome in lung disease. Expert Rev Respir Med 7:245–257 https://doi.org/10.1586/ers.13.24
19	RP Dickson, FJ Martinez, GB Huffnagle (2014) The role of the microbiome in exacerbations of chronic lung diseases. Lancet 384:691–702 https://doi.org/10.1016/S0140-6736(14)61136-3
20	JA DiDonato, F Mercurio, M Karin (2012) NF-kappaB and the link between inflammation and cancer. Immunol Rev 246:379–400 https://doi.org/10.1111/j.1600-065X.2012.01099.x
21	A Dzutsev, JH Badger, E Perez-Chanona, S Roy, R Salcedo, CK Smith, G Trinchieri (2017) Microbes and cancer. Annu Rev Immunol 35:199–228 https://doi.org/10.1146/annurev-immunol-051116-052133
22	E Elinav, R Nowarski, CA Thaiss, B Hu, C, Jin RA Flavell (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13:759–771 https://doi.org/10.1038/nrc3611
23	JR Erb-Downward, DL Thompson, MK Han, CM Freeman, L McCloskey, LA Schmidt, VB Young, GB Toews, JL Curtis, B Sundaramet al. (2011) Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS ONE 6:e16384 https://doi.org/10.1371/journal.pone.0016384
24	WS Garrett (2015) Cancer and the microbiota. Science 348:80–86 https://doi.org/10.1126/science.aaa4972
25	WS Garrett (2019) The gut microbiota and colon cancer. Science 364:1133–1135 https://doi.org/10.1126/science.aaw2367
26	LT Geller, M Barzily-Rokni, T Danino, OH Jonas, N Shental, D Nejman, N Gavert, Y, Zwang ZA Cooper, K Sheeet al. (2017) Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357:1156–1160 https://doi.org/10.1126/science.aah5043
27	S Gomes, B Cavadas, JC Ferreira, PI Marques, C Monteiro, M Sucena, C, Sousa L Vaz Rodrigues, G Teixeira, P Pintoet al. (2019) Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma. Sci Rep 9:12838 https://doi.org/10.1038/s41598-019-49195-w
28	V Gopalakrishnan, CN Spencer, L Nezi, A Reuben, MC Andrews, TV Karpinets, PA Prieto, D Vicente, K Hoffman, SC Weiet al. (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359:97–103 https://doi.org/10.1126/science.aan4236
29	KL Greathouse, JK Stone, CC Harris (2020) Cancer-type-specific bacteria: freeloaders or partners? Cancer Cell 38:158–160 https://doi.org/10.1016/j.ccell.2020.06.017
30	KL Greathouse, JR White, AJ Vargas, VV, Bliskovsky JA Beck, N von Muhlinen, EC Polley, ED Bowman, MA Khan, AI Robleset al. (2018) Interaction between the microbiome and TP53 in human lung cancer. Genome Biol 19:123 https://doi.org/10.1186/s13059-018-1501-6
31	L Guerra, R Guidi, T Frisan (2011) Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression? FEBS J 278:4577–4588 https://doi.org/10.1111/j.1742-4658.2011.08125.x
32	C Gur, Y Ibrahim, B Isaacson, R Yamin, J Abed, M Gamliel, J, Enk Y Bar-On, N Stanietsky-Kaynan, S Coppenhagen-Glazeret al. (2015) Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344–355 https://doi.org/10.1016/j.immuni.2015.01.010
33	AM Gustafson, R Soldi, C Anderlind, MB Scholand, J Qian, X Zhang, K Cooper, D Walker, A McWilliams, G Liuet al. (2010) Airway PI3K pathway activation is an early and reversible event in lung cancer development. Sci Transl Med 2:26ra25 https://doi.org/10.1126/scitranslmed.3000251
34	TJ Hieken, J Chen, TL Hoskin, M Walther-Antonio, S Johnson, S Ramaker, J Xiao, DC Radisky, KL Knutson, KR Kalariet al. (2016) The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep 6:30751 https://doi.org/10.1038/srep30751
35	M Hilty, C Burke, H Pedro, P Cardenas, A Bush, C Bossley, J Davies, A Ervine, L Poulter, L Pachteret al. (2010) Disordered microbial communities in asthmatic airways. PLoS ONE 5:e8578 https://doi.org/10.1371/journal.pone.0008578
36	E Hoste, EN Arwert, R Lal, AP South, JC Salas-Alanis, DF Murrell, G Donati, FM Watt (2015) Innate sensing of microbial products promotes wound-induced skin cancer. Nat Commun 6:5932 https://doi.org/10.1038/ncomms6932
37	GB Huffnagle, RP Dickson, NW Lukacs (2017) The respiratory tract microbiome and lung inflammation: a two-way street. Mucosal Immunol 10:299–306 https://doi.org/10.1038/mi.2016.108
38	Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486:207–214 https://doi.org/10.1038/nature11234
39	N Iida, A Dzutsev, CA Stewart, L Smith, N Bouladoux, RA Weingarten, DA Molina, R Salcedo, T Back, S Crameret al. (2013) Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342:967–970 https://doi.org/10.1126/science.1240527
40	C Jin, GK Lagoudas, C Zhao, S Bullman, A Bhutkar, B Hu, S Ameh, D Sandel, XS Liang, S Mazzilliet al. (2019) Commensal microbiota promote lung cancer development via gammadelta T cells. Cell 176(998–1013):e1016 https://doi.org/10.1016/j.cell.2018.12.040
41	E Kadosh, I Snir-Alkalay, A, Venkatachalam S May, A Lasry, E, Elyada A, Zinger M Shaham, G, Vaalani M Mernbergeret al. (2020) The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Nature 586:133–138 https://doi.org/10.1038/s41586-020-2541-0
42	AD Kostic, E Chun, L Robertson, JN Glickman, CA Gallini, M Michaud, TE Clancy, DC Chung, P Lochhead, GL Holdet al. (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:207–215 https://doi.org/10.1016/j.chom.2013.07.007
43	AD Kostic, D Gevers, CS Pedamallu, M, Michaud F Duke, AM Earl, AI Ojesina, J Jung, AJ Bass, J Taberneroet al. (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res 22:292–298 https://doi.org/10.1101/gr.126573.111
44	V Le Noci, S Guglielmetti, S Arioli, C Camisaschi, F Bianchi, M Sommariva, C Storti, T Triulzi, C Castelli, A Balsariet al. (2018) Modulation of pulmonary microbiota by antibiotic or probiotic aerosol therapy: a strategy to promote immunosurveillance against lung metastases. Cell Rep 24:3528–3538 https://doi.org/10.1016/j.celrep.2018.08.090
45	SH Lee, JY Sung, D Yong, J Chun, SY Kim, JH Song, KS Chung, EY Kim, JY Jung, YA Kanget al. (2016) Characterization of microbiome in bronchoalveolar lavage fluid of patients with lung cancer comparing with benign mass like lesions. Lung Cancer 102:89–95 https://doi.org/10.1016/j.lungcan.2016.10.016
46	RE Ley, DA Peterson, JI Gordon (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124:837–848 https://doi.org/10.1016/j.cell.2006.02.017
47	HX Liu, LL Tao, J Zhang, YG Zhu, Y Zheng, D, Liu M Zhou, H Ke, MM Shi, JM Qu (2018) Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. Int J Cancer 142:769–778 https://doi.org/10.1002/ijc.31098
48	CM Lloyd, BJ Marsland (2017) Lung homeostasis: influence of age, microbes, and the immune system. Immunity 46:549–561 https://doi.org/10.1016/j.immuni.2017.04.005
49	V Matson, J Fessler, R Bao, T Chongsuwat, Y Zha, M-L Alegre, JJ Luke, TF Gajewski (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359:104–108 https://doi.org/10.1126/science.aao3290
50	J, Mrázek C Mekadim, P Kučerová, R Švejstil, H Salmonová, J Vlasáková, R Tarasová, J, Čížková M Červinková(2019) Melanoma-related changes in skin microbiome. Folia Microbiol (Praha) 64:435–442 https://doi.org/10.1007/s12223-018-00670-3
51	T Nakatsuji, TH Chen, AM Butcher, LL Trzoss, SJ Nam, KT Shirakawa, W Zhou, J Oh, M Otto, W Fenicalet al. (2018) A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Sci Adv 4:eaao4502 https://doi.org/10.1126/sciadv.aao4502
52	D Nejman, I, Livyatan G, Fuks N, Gavert Y Zwang, LT Geller, A Rotter-Maskowitz, R Weiser, G, Mallel E Gigiet al. (2020) The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science 368:973–980 https://doi.org/10.1126/science.aay9189
53	J Norenhag, J Du, M Olovsson, H Verstraelen, L Engstrand, N Brusselaers (2020) The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis. BJOG 127:171–180 https://doi.org/10.1111/1471-0528.15854
54	JP Nougayrede, S Homburg, F Taieb, M, Boury E Brzuszkiewicz, G Gottschalk, C Buchrieser, J Hacker, U Dobrindt, E Oswald (2006) Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:848–851 https://doi.org/10.1126/science.1127059
55	DN O’Dwyer, RP Dickson, BB Moore (2016) The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol 196:4839–4847 https://doi.org/10.4049/jimmunol.1600279
56	C Pilette, Y Ouadrhiri, V Godding, JP Vaerman, Y Sibille (2001) Lung mucosal immunity: immunoglobulin—a revisited. Eur Respir J 18:571–588 https://doi.org/10.1183/09031936.01.00228801
57	S Pushalkar, M Hundeyin, D Daley, CP Zambirinis, E Kurz, A Mishra, N Mohan, B Aykut, M Usyk, LE Torreset al. (2018) The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 8:403–416 https://doi.org/10.1158/2159-8290.CD-17-1134
58	J Putze, C Hennequin, JP Nougayrede, W Zhang, S Homburg, H Karch, MA Bringer, C Fayolle, E Carniel, W Rabschet al. (2009) Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect Immun 77:4696–4703 https://doi.org/10.1128/IAI.00522-09
59	AG Ramirez-Labrada, D Isla, A Artal, M Arias, A Rezusta, J, Pardo EM Galvez (2020) The influence of lung microbiota on lung carcinogenesis, immunity, and immunotherapy. Trends Cancer 6:86–97 https://doi.org/10.1016/j.trecan.2019.12.007
60	E Riquelme, Y, Zhang L Zhang, M Montiel, M Zoltan, W Dong, P Quesada, I Sahin, V, Chandra A San Lucaset al. (2019) Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell 178:795–806.e712 https://doi.org/10.1016/j.cell.2019.07.008
61	B Routy, E Le Chatelier, L Derosa, CPM Duong, MT Alou, R, Daillere A, Fluckiger M Messaoudene, C Rauber, MP Robertiet al. (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359:91–97 https://doi.org/10.1126/science.aan3706
62	MR Rubinstein, X Wang, W Liu, Y Hao, G Cai, YW Han (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195–206 https://doi.org/10.1016/j.chom.2013.07.012
63	CL Sears (2009) Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Clin Microbiol Rev 22:349–369 (Table of Contents) https://doi.org/10.1128/CMR.00053-08
64	S Shalapour, M Karin (2020) Cruel to be kind: epithelial, microbial, and immune cell interactions in gastrointestinal cancers. Annu Rev Immunol 38:649–671 https://doi.org/10.1146/annurev-immunol-082019-081656
65	S Shang, F Hua, Z-W Hu (2017) The regulation of β-catenin activity and function in cancer: therapeutic opportunities. OncoTarget 8:33972–33989 https://doi.org/10.18632/oncotarget.15687
66	B Shannon, TJ Yi, S Perusini, P Gajer, B Ma, MS Humphrys, J Thomas-Pavanel, L Chieza, P Janakiram, M Saunderset al. (2017) Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol 10:1310–1319 https://doi.org/10.1038/mi.2016.129
67	Y Shi, W Zheng, K Yang, KG Harris, K Ni, L Xue, W Lin, EB Chang, RR Weichselbaum, YX Fu (2020) Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling. J Exp Med 217(5):e20192282 https://doi.org/10.1084/jem.20192282
68	RL Siegel, KD Miller, A Jemal (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30 https://doi.org/10.3322/caac.21442
69	RL Siegel, KD Miller, A Jemal (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34 https://doi.org/10.3322/caac.21551
70	A Sivan, L Corrales, N Hubert, JB Williams, K Aquino-Michaels, ZM Earley, FW Benyamin, YM Lei, B Jabri, ML Alegreet al. (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084–1089 https://doi.org/10.1126/science.aac4255
71	M Sommariva, V Le Noci, F Bianchi, S Camelliti, A Balsari, E Tagliabue, L Sfondrini(2020) The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy. Cell Mol Life Sci 77:2739–2749 https://doi.org/10.1007/s00018-020-03452-8
72	JE Thorpe, RP Baughman, PT Frame, TA Wesseler, JL Staneck (1987) Bronchoalveolar lavage for diagnosing acute bacterial pneumonia. J Infect Dis 155:855–861 https://doi.org/10.1093/infdis/155.5.855
73	JJ Tsay, BG Wu, MH Badri, JC Clemente, N Shen , P Meyn, Y Li, TA Yie, T, Lhakhang E Olsenet al. (2018) Airway microbiota is associated with upregulation of the PI3K pathway in lung cancer. Am J Respir Crit Care Med 198:1188–1198 https://doi.org/10.1164/rccm.201710-2118OC
74	C Urbaniak, GB Gloor, M Brackstone, L Scott, M, Tangney G Reid (2016) The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol 82:5039–5048 https://doi.org/10.1128/AEM.01235-16
75	M Vétizou, JM Pitt, R Daillère, P Lepage, N Waldschmitt, C Flament, S Rusakiewicz, B Routy, MP Roberti, CPM Duonget al. (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079–1084 https://doi.org/10.1126/science.aad1329
76	S Viaud, F Saccheri, G Mignot, T, Yamazaki R Daillere, D Hannani, DP Enot, C Pfirschke, C Engblom, MJ Pittetet al. (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342:971–976 https://doi.org/10.1126/science.1240537
77	GA Vitiello, DJ Cohen, G Miller (2019) Harnessing the microbiome for pancreatic cancer immunotherapy. Trends Cancer 5:670–676 https://doi.org/10.1016/j.trecan.2019.10.005
78	MR Wilson, Y Jiang, PW Villalta, A Stornetta, PD Boudreau, A Carrá, CA Brennan, E, Chun L Ngo, LD Samsonet al. (2019) The human gut bacterial genotoxin colibactin alkylates DNA. Science 363: eaar7785 https://doi.org/10.1126/science.aar7785
79	K Yamamura, Y Baba, S, Nakagawa K Mima, K Miyake, K Nakamura, H Sawayama, K Kinoshita, T Ishimoto, M Iwatsukiet al. (2016) Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis. Clin Cancer Res 22:5574–5581 https://doi.org/10.1158/1078-0432.CCR-16-1786
80	X Yan, M Yang, J Liu, R Gao, J Hu, J Li, L, Zhang Y, Shi H, Guo J Chenget al. (2015) Discovery and validation of potential bacterial biomarkers for lung cancer. Am J Cancer Res 5:3111–3122
81	G Yu, MH Gail, D Consonni, M Carugno, M Humphrys, AC Pesatori, NE Caporaso, JJ Goedert, J Ravel, MT Landi (2016) Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome Biol 17:163 https://doi.org/10.1186/s13059-016-1021-1
82	T Yu, F Guo, Y Yu, T Sun, D Ma, J Han, Y Qian, I Kryczek, D Sun, N Nagarshethet al. (2017) Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170:548–563.e516 https://doi.org/10.1016/j.cell.2017.07.008

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[2]	Sheng Liu, Wenjing Zhao, Ping Lan, Xiangyu Mou. The microbiome in inflammatory bowel diseases: from pathogenesis to therapy[J]. Protein Cell, 2021, 12(5): 331-345.
[3]	Juanjuan Yuan, Ting Cai, Xiaojun Zheng, Yangzi Ren, Jingwen Qi, Xiaofei Lu, Huihui Chen, Huizhen Lin, Zijie Chen, Mengnan Liu, Shangwen He, Qijun Chen, Siyang Feng, Yingjun Wu, Zhenhai Zhang, Yanqing Ding, Wei Yang. Potentiating CD8⁺ T cell antitumor activity by inhibiting PCSK9 to promote LDLRmediated TCR recycling and signaling[J]. Protein Cell, 2021, 12(4): 240-260.
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[5]	Youqin Xu, Kaiyuan Ji, Meng Wu, Bingtao Hao, Kai-tai Yao, Yang Xu. A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1[J]. Protein Cell, 2019, 10(8): 595-605.
[6]	Tomoaki Hishida, Eric Vazquez-Ferrer, Yuriko Hishida-Nozaki, Ignacio Sancho-Martinez, Yuta Takahashi, Fumiyuki Hatanaka, Jun Wu, Alejandro Ocampo, Pradeep Reddy, Min-Zu Wu, Laurie Gerken, Reuben J. Shaw, Concepcion Rodriguez Esteban, Christopher Benner, Hiroshi Nakagawa, Pedro Guillen Garcia, Estrella Nuñez Delicado, Antoni Castells, Josep M. Campistol, Guang-Hui Liu, Juan Carlos Izpisua Belmonte. Mutations in foregut SOX2⁺ cells induce efficient proliferation via CXCR2 pathway[J]. Protein Cell, 2019, 10(7): 485-495.
[7]	Phei Er Saw, Er-Wei Song. Phage display screening of therapeutic peptide for cancer targeting and therapy[J]. Protein Cell, 2019, 10(11): 787-807.
[8]	Boyi Zhang, Fei Chen, Qixia Xu, Liu Han, Jiaqian Xu, Libin Gao, Xiaochen Sun, Yiwen Li, Yan Li, Min Qian, Yu Sun. Revisiting ovarian cancer microenvironment: a friend or a foe?[J]. Protein Cell, 2018, 9(8): 674-692.
[9]	Faming Zhang, Bota Cui, Xingxiang He, Yuqiang Nie, Kaichun Wu, Daiming Fan, FMT-standardization Study Group. Microbiota transplantation: concept, methodology and strategy for its modernization[J]. Protein Cell, 2018, 9(5): 462-473.
[10]	Marwah Doestzada, Arnau Vich Vila, Alexandra Zhernakova, Debby P. Y. Koonen, Rinse K. Weersma, Daan J. Touw, Folkert Kuipers, Cisca Wijmenga, Jingyuan Fu. Pharmacomicrobiomics: a novel route towards personalized medicine?[J]. Protein Cell, 2018, 9(5): 432-445.
[11]	Jun Wang, Liang Chen, Na Zhao, Xizhan Xu, Yakun Xu, Baoli Zhu. Of genes and microbes: solving the intricacies in host genomes[J]. Protein Cell, 2018, 9(5): 446-461.
[12]	Lu Gao, Tiansong Xu, Gang Huang, Song Jiang, Yan Gu, Feng Chen. Oral microbiomes: more and more importance in oral cavity and whole body[J]. Protein Cell, 2018, 9(5): 488-500.
[13]	Yu Ping, Chaojun Liu, Yi Zhang. T-cell receptor-engineered T cells for cancer treatment: current status and future directions[J]. Protein Cell, 2018, 9(3): 254-266.
[14]	Yuanyuan Gu, Shuoxin Liu, Xiaodan Zhang, Guimin Chen, Hongwei Liang, Mengchao Yu, Zhicong Liao, Yong Zhou, Chen-Yu Zhang, Tao Wang, Chen Wang, Junfeng Zhang, Xi Chen. Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer[J]. Protein Cell, 2017, 8(6): 455-466.
[15]	Yingjiao Xue,Shenda Hou,Hongbin Ji,Xiangkun Han. Evolution from genetics to phenotype: reinterpretation of NSCLC plasticity, heterogeneity, and drug resistance[J]. Protein Cell, 2017, 8(3): 178-190.

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