Microbial Allies: How Gut Microbiota Influence the Effectiveness of Immune Checkpoint Inhibitors

Azhdari Tehrani, Hamed; Yousefi, Amir-Mohammad; Salari, Sina; Bashash, Davood

doi:10.61186/ijbc.16.3.70

Volume 16, Issue 3 (September 2024 2024) Iranian Journal of Blood and Cancer 2024, 16(3): 70-85 | Back to browse issues page

‎ 10.61186/ijbc.16.3.70

Mendeley

Zotero

RefWorks

Azhdari Tehrani H, Yousefi A, Salari S, Bashash D. Microbial Allies: How Gut Microbiota Influence the Effectiveness of Immune Checkpoint Inhibitors. Iranian Journal of Blood and Cancer 2024; 16 (3) :70-85
URL: http://ijbc.ir/article-1-1576-en.html

Microbial Allies: How Gut Microbiota Influence the Effectiveness of Immune Checkpoint Inhibitors

Hamed Azhdari Tehrani¹

, Amir-Mohammad Yousefi²

, Sina Salari³

, Davood Bashash ^*⁴

1- Department of Hematology-Medical oncology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3- Department of Hematology-oncology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran , david_5980@yahoo.com

Abstract: (483 Views)

The importance of the gut microbiota in human health and disease has been known for a long time. Current investigations involving preclinical and clinical studies have presented numerous lines of evidence indicating that gut microbiota can influence the effectiveness of cancer immunotherapies, particularly immune checkpoint inhibitors (ICIs). The gut microbiota can alter the immune response in the tumor microenvironment (TME) by engaging with innate and adaptive immune cells. Notably, one of the primary methods by which the gut microbiota modulates antitumor immunity is through the production of metabolites, which are small molecules capable of traveling from the gut to other parts of the body and influencing local and systemic antitumor immune responses. This exploration of mechanisms has yielded valuable insights for developing microbiota-based therapeutic strategies such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites. In this review, we explored several possible interventions that could enhance the efficacy of ICIs, thereby potentially restoring or augmenting patient responses to these therapeutic agents.

Keywords: Gut microbiota, Immunotherapy, Immune checkpoint inhibitors, ICIs, Cancer

Full-Text [PDF 756 kb] (200 Downloads)

: Review Article | Subject: Microbiome in Cancer
Received: 2024/07/4 | Accepted: 2024/09/12 | Published: 2024/09/30

References

1. Fan Y, Xie W, Huang H, Wang Y, Li G, Geng Y, et al. Association of immune related adverse events with efficacy of immune checkpoint inhibitors and overall survival in cancers: a systemic review and meta-analysis. Frontiers in Oncology. 2021;11:633032. [DOI:10.3389/fonc.2021.633032]

2. Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annual Review of Pathology: Mechanisms of Disease. 2021;16:223-49. [DOI:10.1146/annurev-pathol-042020-042741]

3. Vanderwalde A, Spetzler D, Xiao N, Gatalica Z, Marshall J. Microsatellite instability status determined by next‐generation sequencing and compared with PD‐L1 and tumor mutational burden in 11,348 patients. Cancer medicine. 2018;7(3):746-56. [DOI:10.1002/cam4.1372]

4. Park EM, Chelvanambi M, Bhutiani N, Kroemer G, Zitvogel L, Wargo JA. Targeting the gut and tumor microbiota in cancer. Nature medicine. 2022;28(4):690-703. [DOI:10.1038/s41591-022-01779-2]

5. Ijsselsteijn R, Jansen JG, de Wind N. DNA mismatch repair-dependent DNA damage responses and cancer. DNA repair. 2020;93:102923. [DOI:10.1016/j.dnarep.2020.102923]

6. Mestrallet G, Brown M, Bozkus CC, Bhardwaj N. Immune escape and resistance to immunotherapy in mismatch repair deficient tumors. Frontiers in Immunology. 2023;14:1210164. [DOI:10.3389/fimmu.2023.1210164]

7. Yang Y, Li X, Ma Z, Wang C, Yang Q, Byrne-Steele M, et al. CTLA-4 expression by B-1a B cells is essential for immune tolerance. Nature communications. 2021;12(1):525. [DOI:10.1038/s41467-020-20874-x]

8. Ghosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. Journal of Cancer. 2021;12(9):2735. [DOI:10.7150/jca.57334]

9. Pauken KE, Torchia JA, Chaudhri A, Sharpe AH, Freeman GJ, editors. Emerging concepts in PD-1 checkpoint biology. Seminars in immunology; 2021: Elsevier. [DOI:10.1016/j.smim.2021.101480]

10. Sondak VK, Smalley KS, Kudchadkar R, Grippon S, Kirkpatrick P. Ipilimumab. Nature reviews Drug discovery. 2011;10(6):411-2. [DOI:10.1038/nrd3463]

11. Lax BM, Palmeri JR, Lutz EA, Sheen A, Stinson JA, Duhamel L, et al. Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies. Proceedings of the National Academy of Sciences of the United States of America. 2023;120(31):e2300895120. [DOI:10.1073/pnas.2300895120]

12. Wong SK, Beckermann KE, Johnson DB, Das S. Combining anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) and -programmed cell death protein 1 (PD-1) agents for cancer immunotherapy. Expert opinion on biological therapy. 2021;21(12):1623-34. [DOI:10.1080/14712598.2021.1921140]

13. Keytruda (pembrolizumab) prescribing information [Internet] Whitehouse Station (NJ): Merck & Co., Inc; 2014. [cited 2014 Oct 23]. 12p. Available from: http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. [Google Scholar].

14. Opdivo (nivolumab) prescribing information [Internet]. Princeton (NJ): Bristol-Myers Squibb Company; 2015. [cited 2015 Jan 27]. 8p. Available from: http://packageinserts.bms.com/pi/pi_opdivo.pdf. [Google Scholar].

15. Zhang Q, Huo G-w, Zhang H-z, Song Y. Efficacy of pembrolizumab for advanced/metastatic melanoma: a meta-analysis. Open Medicine. 2020;15(1):447-56. [DOI:10.1515/med-2020-0110]

16. Hodi FS, Postow MA, Chesney JA, Pavlick AC, Robert C, Grossmann KF, et al. Clinical response, progression-free survival (PFS), and safety in patients (pts) with advanced melanoma (MEL) receiving nivolumab (NIVO) combined with ipilimumab (IPI) vs IPI monotherapy in CheckMate 069 study. American Society of Clinical Oncology; 2015. [DOI:10.1200/jco.2015.33.15_suppl.9004]

17. Mok TS, Wu Y-L, Kudaba I, Kowalski DM, Cho BC, Turna HZ, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. The Lancet. 2019;393(10183):1819-30. [DOI:10.1016/S0140-6736(18)32409-7]

18. Reck M, Rodríguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A, et al. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. 2019. [DOI:10.1200/JCO.18.00149]

19. Tang Q, Li S, Huang G, Liu H. Research progress on PD-1 and PD-L1 inhibitors in the treatment of metastatic urothelial carcinoma. International Immunopharmacology. 2023;119:110158. [DOI:10.1016/j.intimp.2023.110158]

20. Yu L, Xu J, Qiao R, Han B, Zhong H, Zhong R. Efficacy and safety of anlotinib combined with PD‐1/PD‐L1 inhibitors as second‐line and subsequent therapy in advanced small‐cell lung cancer. Cancer Medicine. 2023;12(5):5372-83. [DOI:10.1002/cam4.5360]

21. Fasano M, Della Corte CM, Di Liello R, Barra G, Sparano F, Viscardi G, et al. Induction of natural killer antibody-dependent cell cytotoxicity and of clinical activity of cetuximab plus avelumab in non-small cell lung cancer. Esmo Open. 2020;5(5):e000753. [DOI:10.1136/esmoopen-2020-000753]

22. Walker AW, Hoyles L. Human microbiome myths and misconceptions. Nature Microbiology. 2023;8(8):1392-6. [DOI:10.1038/s41564-023-01426-7]

23. Barone M, D'Amico F, Brigidi P, Turroni S. Gut microbiome-micronutrient interaction: The key to controlling the bioavailability of minerals and vitamins? Biofactors. 2022;48(2):307-14. [DOI:10.1002/biof.1835]

24. Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell research. 2020;30(6):492-506. [DOI:10.1038/s41422-020-0332-7]

25. Borbet TC, Pawline MB, Li J, Ho ML, Yin YS, Zhang X, et al. Disruption of the early-life microbiota alters Peyer's patch development and germinal center formation in gastrointestinal-associated lymphoid tissue. Iscience. 2023;26(6). [DOI:10.1016/j.isci.2023.106810]

26. Sun C-Y, Yang N, Zheng Z-L, Liu D, Xu Q-L. T helper 17 (Th17) cell responses to the gut microbiota in human diseases. Biomedicine & Pharmacotherapy. 2023;161:114483. [DOI:10.1016/j.biopha.2023.114483]

27. Bugl S, Wirths S, Müller MR, Radsak MP, Kopp HG. Current insights into neutrophil homeostasis. Annals of the New York Academy of Sciences. 2012;1266(1):171-8. [DOI:10.1111/j.1749-6632.2012.06607.x]

28. Strowig T, Thiemann S, Diefenbach A. Microbiome and gut immunity: innate immune cells. The Gut Microbiome in Health and Disease. 2018:103-18. [DOI:10.1007/978-3-319-90545-7_8]

29. Jiménez-Saiz R, Anipindi VC, Ellenbogen Y, Koenig JF, Chu DK, Ask K, et al. Microbial regulation of enteric eosinophils and its impact on tissue remodeling and Th2 immunity. Frontiers in Immunology. 2020;11:500585. [DOI:10.3389/fimmu.2020.00155]

30. Lee C, Lee H, Park JC, Im S-H. Microbial components and effector molecules in T helper cell differentiation and function. Immune Network. 2023;23(1). [DOI:10.4110/in.2023.23.e7]

31. Mashiah J, Karady T, Fliss‐Isakov N, Sprecher E, Slodownik D, Artzi O, et al. Clinical efficacy of fecal microbial transplantation treatment in adults with moderate‐to‐severe atopic dermatitis. Immunity, inflammation and disease. 2022;10(3):e570. [DOI:10.1002/iid3.570]

32. Fang Z, Li L, Zhao J, Zhang H, Lee Y-K, Lu W, et al. Bifidobacteria adolescentis regulated immune responses and gut microbial composition to alleviate DNFB-induced atopic dermatitis in mice. European Journal of Nutrition. 2020;59:3069-81. [DOI:10.1007/s00394-019-02145-8]

33. Kwon M-S, Roh SW, Choi H-J. Lactobacillus sakei WIKIM30 ameliorates atopic dermatitis-like skin lesions by inducing regulatory T cells and altering gut microbiota structure in mice. Frontiers in immunology. 2018;9:402989. [DOI:10.3389/fimmu.2018.01905]

34. Li T, Ma X, Wang T, Tian W, Liu J, Shen W, et al. Clostridium butyricum Inhibits the Inflammation in Children with Primary Nephrotic Syndrome by Regulating Th17/Tregs Balance via Gut-Kidney Axis. 2023. [DOI:10.21203/rs.3.rs-3619181/v1]

35. Omenetti S, Pizarro TT. The Treg/Th17 axis: a dynamic balance regulated by the gut microbiome. Frontiers in immunology. 2015;6:168417. [DOI:10.3389/fimmu.2015.00639]

36. Amy IY, Zhao L, Eaton KA, Ho S, Chen J, Poe S, et al. Gut microbiota modulate CD8 T cell responses to influence colitis-associated tumorigenesis. Cell reports. 2020;31(1). [DOI:10.1016/j.celrep.2020.03.035]

37. Pabst O, Nowosad CR, editors. B cells and the intestinal microbiome in time, space and place. Seminars in Immunology; 2023: Elsevier. [DOI:10.1016/j.smim.2023.101806]

38. Nowosad CR, Mesin L, Castro TB, Wichmann C, Donaldson GP, Araki T, et al. Tunable dynamics of B cell selection in gut germinal centres. Nature. 2020;588(7837):321-6. [DOI:10.1038/s41586-020-2865-9]

39. Li H, Limenitakis JP, Greiff V, Yilmaz B, Schären O, Urbaniak C, et al. Mucosal or systemic microbiota exposures shape the B cell repertoire. Nature. 2020;584(7820):274-8. [DOI:10.1038/s41586-020-2564-6]

40. De Filippis F, Paparo L, Nocerino R, Della Gatta G, Carucci L, Russo R, et al. Specific gut microbiome signatures and the associated pro-inflamatory functions are linked to pediatric allergy and acquisition of immune tolerance. Nature Communications. 2021;12(1):5958. [DOI:10.1038/s41467-021-26266-z]

41. Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079-84. [DOI:10.1126/science.aad1329]

42. Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084-9. [DOI:10.1126/science.aac4255]

43. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews M, Karpinets T, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. [DOI:10.1126/science.aan4236]

44. Routy B, Le Chatelier E, Derosa L, Duong CP, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-7. [DOI:10.1126/science.aan3706]

45. Schaupp L, Muth S, Rogell L, Kofoed-Branzk M, Melchior F, Lienenklaus S, et al. Microbiota-induced type I interferons instruct a poised basal state of dendritic cells. Cell. 2020;181(5):1080-96. e19. [DOI:10.1016/j.cell.2020.04.022]

46. Kalafati L, Kourtzelis I, Schulte-Schrepping J, Li X, Hatzioannou A, Grinenko T, et al. Innate immune training of granulopoiesis promotes anti-tumor activity. Cell. 2020;183(3):771-85. e12. [DOI:10.1016/j.cell.2020.09.058]

47. Lam KC, Araya RE, Huang A, Chen Q, Di Modica M, Rodrigues RR, et al. Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment. Cell. 2021;184(21):5338-56. e21. [DOI:10.1016/j.cell.2021.09.019]

48. Deng H, Li Z, Tan Y, Guo Z, Liu Y, Wang Y, et al. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages. Scientific reports. 2016;6(1):29401. [DOI:10.1038/srep29401]

49. Böttcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M, Sammicheli S, et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell. 2018;172(5):1022-37. e14. [DOI:10.1016/j.cell.2018.01.004]

50. Jin Y, Dong H, Xia L, Yang Y, Zhu Y, Shen Y, et al. The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC. Journal of Thoracic Oncology. 2019;14(8):1378-89. [DOI:10.1016/j.jtho.2019.04.007]

51. Qiu Y, Jiang Z, Hu S, Wang L, Ma X, Yang X. Lactobacillus plantarum enhanced IL-22 production in natural killer (NK) cells that protect the integrity of intestinal epithelial cell barrier damaged by enterotoxigenic Escherichia coli. International Journal of Molecular Sciences. 2017;18(11):2409. [DOI:10.3390/ijms18112409]

52. Rizvi ZA, Dalal R, Sadhu S, Kumar Y, Kumar S, Gupta SK, et al. High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity. Science Advances. 2021;7(37):eabg5016. [DOI:10.1126/sciadv.abg5016]

53. Myers JA, Miller JS. Exploring the NK cell platform for cancer immunotherapy. Nature reviews Clinical oncology. 2021;18(2):85-100. [DOI:10.1038/s41571-020-0426-7]

54. Nicolai CJ, Wolf N, Chang I-C, Kirn G, Marcus A, Ndubaku CO, et al. NK cells mediate clearance of CD8+ T cell-resistant tumors in response to STING agonists. Science immunology. 2020;5(45):eaaz2738. [DOI:10.1126/sciimmunol.aaz2738]

55. Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602-9. [DOI:10.1126/science.abb5920]

56. Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W, Sugiura Y, et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature. 2019;565(7741):600-5. [DOI:10.1038/s41586-019-0878-z]

57. Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Annals of Oncology. 2017;28(6):1368-79. [DOI:10.1093/annonc/mdx108]

58. Mager LF, Burkhard R, Pett N, Cooke NC, Brown K, Ramay H, et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science. 2020;369(6510):1481-9. [DOI:10.1126/science.abc3421]

59. Kikuchi T, Mimura K, Ashizawa M, Okayama H, Endo E, Saito K, et al. Characterization of tumor-infiltrating immune cells in relation to microbiota in colorectal cancers. Cancer Immunology, Immunotherapy. 2020;69:23-32. [DOI:10.1007/s00262-019-02433-6]

60. Jain T, Dudeja V. New insights into the cancer-microbiome-immune axis: decrypting a decade of discoveries. Frontiers in immunology. 2021;12:622064. [DOI:10.3389/fimmu.2021.622064]

61. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M-L, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104-8. [DOI:10.1126/science.aao3290]

62. Xu X, Lv J, Guo F, Li J, Jia Y, Jiang D, et al. Gut microbiome influences the efficacy of PD-1 antibody immunotherapy on MSS-type colorectal cancer via metabolic pathway. Frontiers in Microbiology. 2020;11:814. [DOI:10.3389/fmicb.2020.00814]

63. Coutzac C, Jouniaux J-M, Paci A, Schmidt J, Mallardo D, Seck A, et al. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nature communications. 2020;11(1):2168. [DOI:10.1038/s41467-020-16079-x]

64. Dees KJ, Koo H, Humphreys JF, Hakim JA, Crossman DK, Crowley MR, et al. Human gut microbial communities dictate efficacy of anti-PD-1 therapy in a humanized microbiome mouse model of glioma. Neuro-oncology advances. 2021;3(1):vdab023. [DOI:10.1093/noajnl/vdab023]

65. Gao G, Ma T, Zhang T, Jin H, Li Y, Kwok LY, et al. Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota. Front Immunol. 2021;12:772532. [DOI:10.3389/fimmu.2021.772532]

66. Messaoudene M, Pidgeon R, Richard C, Ponce M, Diop K, Benlaifaoui M, et al. A Natural Polyphenol Exerts Antitumor Activity and Circumvents Anti-PD-1 Resistance through Effects on the Gut Microbiota. Cancer Discov. 2022;12(4):1070-87. [DOI:10.1158/2159-8290.CD-21-0808]

67. Fong W, Li Q, Ji F, Liang W, Lau HCH, Kang X, et al. Lactobacillus gallinarum-derived metabolites boost anti-PD1 efficacy in colorectal cancer by inhibiting regulatory T cells through modulating IDO1/Kyn/AHR axis. Gut. 2023. [DOI:10.1016/S0016-5085(23)01173-3]

68. Passaro A, Brahmer J, Antonia S, Mok T, Peters S. Managing resistance to immune checkpoint inhibitors in lung cancer: treatment and novel strategies. Journal of Clinical Oncology. 2022. [DOI:10.1200/JCO.21.01845]

69. Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28(6):1368-79. [DOI:10.1093/annonc/mdx108]

70. Derosa L, Routy B, Fidelle M, Iebba V, Alla L, Pasolli E, et al. Gut bacteria composition drives primary resistance to cancer immunotherapy in renal cell carcinoma patients. European urology. 2020;78(2):195-206. [DOI:10.1016/j.eururo.2020.04.044]

71. Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, Friard S, et al. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nature medicine. 2022;28(2):315-24. [DOI:10.1038/s41591-021-01655-5]

72. Goubet A-G, Wheeler R, Fluckiger A, Qu B, Lemaître F, Iribarren K, et al. Multifaceted modes of action of the anticancer probiotic Enterococcus hirae. Cell Death & Differentiation. 2021;28(7):2276-95. [DOI:10.1038/s41418-021-00753-8]

73. Wu Q, Liu J, Wu S, Xie X. The impact of antibiotics on efficacy of immune checkpoint inhibitors in malignancies: A study based on 44 cohorts. Int Immunopharmacol. 2021;92:107303. [DOI:10.1016/j.intimp.2020.107303]

74. Ahmed J, Kumar A, Parikh K, Anwar A, Knoll BM, Puccio C, et al. Use of broad-spectrum antibiotics impacts outcome in patients treated with immune checkpoint inhibitors. Oncoimmunology. 2018;7(11):e1507670. [DOI:10.1080/2162402X.2018.1507670]

75. Pinato DJ, Howlett S, Ottaviani D, Urus H, Patel A, Mineo T, et al. Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer. JAMA Oncology. 2019;5(12):1774-8. [DOI:10.1001/jamaoncol.2019.2785]

76. Tinsley N, Zhou C, Tan G, Rack S, Lorigan P, Blackhall F, et al. Cumulative Antibiotic Use Significantly Decreases Efficacy of Checkpoint Inhibitors in Patients with Advanced Cancer. Oncologist. 2020;25(1):55-63. [DOI:10.1634/theoncologist.2019-0160]

77. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. [DOI:10.1126/science.aan4236]

78. Ademe M. Benefits of fecal microbiota transplantation: A comprehensive review. The Journal of Infection in Developing Countries. 2020;14(10):1074-80. [DOI:10.3855/jidc.12780]

79. Quraishi MN, Widlak M, Bhala Na, Moore D, Price M, Sharma N, et al. Systematic review with meta‐analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Alimentary pharmacology & therapeutics. 2017;46(5):479-93. [DOI:10.1111/apt.14201]

80. Biancheri P, Divekar D, Watson AJ. Could fecal transplantation become part of PD-1-based immunotherapy, due to effects of the intestinal microbiome? Gastroenterology. 2018;154(6):1845-7. [DOI:10.1053/j.gastro.2018.03.060]

81. Genton L, Lazarevic V, Stojanovic O, Spiljar M, Djaafar S, Koessler T, et al. Metataxonomic and metabolic impact of fecal microbiota transplantation from patients with pancreatic cancer into germ-free mice: A pilot study. Frontiers in cellular and infection microbiology. 2021;11:752889. [DOI:10.3389/fcimb.2021.752889]

82. Wang Y, Varatharajalu K, Shatila M, Thomas A, Campbell M, Msaouel P, et al. S227 First-Line Treatment of Fecal Microbiota Transplantation for Immune-Mediated Colitis. Official journal of the American College of Gastroenterology| ACG. 2023;118(10S):S170. [DOI:10.14309/01.ajg.0000950548.93113.83]

83. Rapoport EA, Baig M, Puli SR. Adverse events in fecal microbiota transplantation: a systematic review and meta-analysis. Annals of Gastroenterology. 2022;35(2):150. [DOI:10.20524/aog.2022.0695]

84. Nguyen TL, Vieira-Silva S, Liston A, Raes J. How informative is the mouse for human gut microbiota research? Dis Model Mech. 2015;8(1):1-16. [DOI:10.1242/dmm.017400]

85. Ciernikova S, Sevcikova A, Drgona L, Mego M. Modulating the gut microbiota by probiotics, prebiotics, postbiotics, and fecal microbiota transplantation: An emerging trend in cancer patient care. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2023:188990. [DOI:10.1016/j.bbcan.2023.188990]

86. Canale FP, Basso C, Antonini G, Perotti M, Li N, Sokolovska A, et al. Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature. 2021;598(7882):662-6. [DOI:10.1038/s41586-021-04003-2]

87. Bevilacqua A, Campaniello D, Speranza B, Racioppo A, Sinigaglia M, Corbo MR. An Update on Prebiotics and on Their Health Effects. Foods. 2024;13(3):446. [DOI:10.3390/foods13030446]

88. Taper HS, Roberfroid MB. Possible adjuvant cancer therapy by two prebiotics-inulin or oligofructose. In vivo. 2005;19(1):201-4.

Send email to the article author

Rights and permissions
	This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb