Abstract
Significant advances have been made in the past decade across the melanoma care continuum, with approved systemic therapy for patients with advanced disease as well as in the adjuvant setting. We are gaining an appreciation of the factors that drive response and resistance to these therapies, and there is novel evidence that the microbiome (which refers to the microbes that inhabit our bodies along with their collective genomes) may shape overall immunity and may even impact therapeutic responses (e.g., immune checkpoint blockade). This has profound implications and calls to question if the microbiome could be used as a biomarker or therapeutic target in patients going onto treatment with immune checkpoint blockade (and potentially onto other forms of therapy). Insights are also being gained into the potential influence of the microbiota on melanoma development at the level of the skin and of the gut, though there is a tremendous knowledge yet to be gained. Each of these aspects will be discussed herein, as will strategies to target and factors that influence the microbiome.
Keywords
- Melanoma
- Microbiome
- Checkpoint blockade
- Immunity
This is a preview of subscription content, access via your institution.
References
Abedon ST et al (2017) Editorial: phage therapy: past, present and future. Front Microbiol 8:981
Alekseyenko AV et al (2013) Community differentiation of the cutaneous microbiota in psoriasis. Microbiome 1(1):31
Baker BS, Powles A, Fry L (2006) Peptidoglycan: a major aetiological factor for psoriasis? Trends Immunol 27(12):545–551
Belkaid Y, Segre JA (2014) Dialogue between skin microbiota and immunity. Science 346(6212):954–959
Bhatt AP, Redinbo MR, Bultman SJ (2017) The role of the microbiome in cancer development and therapy. CA Cancer J Clin 67(4):326–344
Boursi B et al (2015) Recurrent antibiotic exposure may promote cancer formation – another step in understanding the role of the human microbiota? Eur J Cancer 51(17):2655–2664
Boyman O et al (2007) The pathogenic role of tissue-resident immune cells in psoriasis. Trends Immunol 28(2):51–57
Budynek P et al (2010) Bacteriophages and cancer. Arch Microbiol 192(5):315–320
Bullman S et al (2017) Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 358(6369):1443–1448
Byrd AL, Belkaid Y, Segre JA (2018) The human skin microbiome. Nat Rev Microbiol 16(3):143–155
Caporaso JG et al (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7(5):335–336
Castellarin M et al (2012) Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res 22(2):299–306
Chaput N et al (2017) Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol 28(6):1368–1379
Chen YE, Fischbach MA, Belkaid Y (2018) Skin microbiota-host interactions. Nature 553(7689):427–436
Cogdill AP et al (2018) The impact of intratumoral and gastrointestinal microbiota on systemic cancer therapy. Trends Immunol 39(11):900–920
Conrad C et al (2007) Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat Med 13(7):836–842
Dalmasso G et al (2014) The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes 5(5):675–680
Davison SC et al (2001) Contrasting patterns of streptococcal superantigen-induced T-cell proliferation in guttate vs. chronic plaque psoriasis. Br J Dermatol 145(2):245–251
De Benedetto A, Kubo A, Beck LA (2012) Skin barrier disruption: a requirement for allergen sensitization? J Invest Dermatol 132(3 Pt 2):949–963
Derosa L et al (2018) Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann Oncol 29(6):1437–1444
Drago L et al (2016) Skin microbiota of first cousins affected by psoriasis and atopic dermatitis. Clin Mol Allergy 14:2
Duncan SH, Louis P, Flint HJ (2007) Cultivable bacterial diversity from the human colon. Lett Appl Microbiol 44(4):343–350
Eckburg PB et al (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638
Eiseman B et al (1958) Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 44(5):854–859
Fahlen A et al (2012) Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin. Arch Dermatol Res 304(1):15–22
Frankel AE et al (2017) Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia 19(10):848–855
Frosali S et al (2015) How the intricate interaction among toll-like receptors, microbiota, and intestinal immunity can influence gastrointestinal pathology. J Immunol Res 2015:489821
Fry L, Baker BS (2007) Triggering psoriasis: the role of infections and medications. Clin Dermatol 25(6):606–615
Furusawa Y et al (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446–450
Gao Z et al (2007) Molecular analysis of human forearm superficial skin bacterial biota. Proc Natl Acad Sci U S A 104(8):2927–2932
Gao Z et al (2008) Substantial alterations of the cutaneous bacterial biota in psoriatic lesions. PLoS One 3(7):e2719
Garcia-Castillo V et al (2016) Microbiota dysbiosis: a new piece in the understanding of the carcinogenesis puzzle. J Med Microbiol 65(12):1347–1362
Garrett WS (2015) Cancer and the microbiota. Science 348(6230):80–86
Geller LT et al (2017) Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science 357(6356):1156–1160
Gopalakrishnan V et al (2018a) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359(6371):97–103
Gopalakrishnan V et al (2018b) The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell 33(4):570–580
Gough E, Shaikh H, Manges AR (2011) Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 53(10):994–1002
Grice EA (2014) The skin microbiome: potential for novel diagnostic and therapeutic approaches to cutaneous disease. Semin Cutan Med Surg 33(2):98–103
Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9(4):244–253
He Z et al (2018) Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut 68:289–300
Hibberd AA et al (2017) Intestinal microbiota is altered in patients with colon cancer and modified by probiotic intervention. BMJ Open Gastroenterol 4(1):e000145
Honda K, Littman DR (2016) The microbiota in adaptive immune homeostasis and disease. Nature 535(7610):75–84
Human Microbiome Project Consortium (2012a) A framework for human microbiome research. Nature 486(7402):215–221
Human Microbiome Project Consortium (2012b) Structure, function and diversity of the healthy human microbiome. Nature 486(7402):207–214
Johansson ME et al (2015) Normalization of host intestinal mucus layers requires long-term microbial colonization. Cell Host Microbe 18(5):582–592
Juul FE et al (2018) Fecal microbiota transplantation for primary Clostridium difficile infection. N Engl J Med 378(26):2535–2536
Khanna S et al (2016) Gut microbiome predictors of treatment response and recurrence in primary Clostridium difficile infection. Aliment Pharmacol Ther 44(7):715–727
Kim D, Zeng MY, Nunez G (2017) The interplay between host immune cells and gut microbiota in chronic inflammatory diseases. Exp Mol Med 49(5):e339
Kostic AD et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2):207–215
Kroemer G, Zitvogel L (2018) Cancer immunotherapy in 2017: the breakthrough of the microbiota. Nat Rev Immunol 18(2):87–88
Lagier JC et al (2012) Microbial culturomics: paradigm shift in the human gut microbiome study. Clin Microbiol Infect 18(12):1185–1193
Lagier JC et al (2018) Culturing the human microbiota and culturomics. Nat Rev Microbiol 16:540–550
Lathrop SK et al (2011) Peripheral education of the immune system by colonic commensal microbiota. Nature 478(7368):250–254
Linehan JL et al (2018) Non-classical immunity controls microbiota impact on skin immunity and tissue repair. Cell 172(4):784–796.e18
Littman AJ et al (2004) Chlamydia pneumoniae infection and risk of lung cancer. Cancer Epidemiol Biomark Prev 13(10):1624–1630
Lloyd-Price J, Abu-Ali G, Huttenhower C (2016) The healthy human microbiome. Genome Med 8(1):51
Lusiak-Szelachowska M et al (2017) Bacteriophages in the gastrointestinal tract and their implications. Gut Pathog 9:44
Mangerich A et al (2012) Infection-induced colitis in mice causes dynamic and tissue-specific changes in stress response and DNA damage leading to colon cancer. Proc Natl Acad Sci U S A 109(27):E1820–E1829
Matson V et al (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359(6371):104–108
McCoy AN et al (2013) Fusobacterium is associated with colorectal adenomas. PLoS One 8(1):e53653
McDonald D et al (2018) American Gut: an open platform for citizen science microbiome research. mSystems 3(3):e00031–18. PMID: 29795809
McFadden J, Valdimarsson H, Fry L (1991) Cross-reactivity between streptococcal M surface antigen and human skin. Br J Dermatol 125(5):443–447
Miller NJ et al (2018) Merkel cell polyomavirus-specific immune responses in patients with Merkel cell carcinoma receiving anti-PD-1 therapy. J Immunother Cancer 6(1):131
Mima K et al (2015) Fusobacterium nucleatum and T cells in colorectal carcinoma. JAMA Oncol 1(5):653–661
Mima K et al (2017) The microbiome and hepatobiliary-pancreatic cancers. Cancer Lett 402:9–15
Nagy KN et al (1998) The microflora associated with human oral carcinomas. Oral Oncol 34(4):304–308
Nestle FO, Kaplan DH, Barker J (2009) Psoriasis. N Engl J Med 361(5):496–509
Oude Griep LM, Wang H, Chan Q (2013) Empirically-derived dietary patterns, diet quality scores, and markers of inflammation and endothelial dysfunction. Curr Nutr Rep 2(2):97–104
Pace NR (1997) A molecular view of microbial diversity and the biosphere. Science 276(5313):734–740
Paramsothy S et al (2017) Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet 389(10075):1218–1228
Peek RM Jr, Blaser MJ (2002) Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer 2(1):28–37
Pranjol MZ, Hajitou A (2015) Bacteriophage-derived vectors for targeted cancer gene therapy. Viruses 7(1):268–284
Purcell RV et al (2017) Colonization with enterotoxigenic Bacteroides fragilis is associated with early-stage colorectal neoplasia. PLoS One 12(2):e0171602
Ramirez-Farias C et al (2009) Effect of inulin on the human gut microbiota: stimulation of Bifidobacterium adolescentis and Faecalibacterium prausnitzii. Br J Nutr 101(4):541–550
Rao K, Young VB (2015) Fecal microbiota transplantation for the management of Clostridium difficile infection. Infect Dis Clin N Am 29(1):109–122
Reichardt N et al (2014) Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J 8(6):1323–1335
Rieckmann T et al (2013) HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol 107(2):242–246
Rosenberg SA et al (2008) Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nat Rev Cancer 8(4):299–308
Routy B et al (2017) The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation. Oncoimmunology 6(1):e1258506
Routy B et al (2018a) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359(6371):91–97
Routy B et al (2018b) The gut microbiota influences anticancer immunosurveillance and general health. Nat Rev Clin Oncol 15(6):382–396
Rubinstein MR et al (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14(2):195–206
Sanford JA, Gallo RL (2013) Functions of the skin microbiota in health and disease. Semin Immunol 25(5):370–377
Sears CL, Garrett WS (2014) Microbes, microbiota, and colon cancer. Cell Host Microbe 15(3):317–328
Sekirov I et al (2010) Gut microbiota in health and disease. Physiol Rev 90(3):859–904
Seng P et al (2009) Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Infect Dis 49(4):543–551
Sheflin AM, Whitney AK, Weir TL (2014) Cancer-promoting effects of microbial dysbiosis. Curr Oncol Rep 16(10):406
Shendure J, Ji H (2008) Next-generation DNA sequencing. Nat Biotechnol 26(10):1135–1145
Sivan A et al (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089
Smola S (2017) Immunopathogenesis of HPV-associated cancers and prospects for immunotherapy. Viruses 9(9). pii:E254. PMID: 28895886
Spiljar M, Merkler D, Trajkovski M (2017) The immune system bridges the gut microbiota with systemic energy homeostasis: focus on TLRs, mucosal barrier, and SCFAs. Front Immunol 8:1353
Staley JT, Konopka A (1985) Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu Rev Microbiol 39:321–346
Strati F et al (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5(1):24
Suez J et al (2018) Post-antibiotic gut mucosal microbiome reconstitution is impaired by probiotics and improved by autologous FMT. Cell 174(6):1406–1423.e16
Tang WH, Kitai T, Hazen SL (2017) Gut microbiota in cardiovascular health and disease. Circ Res 120(7):1183–1196
Tashiro H, Brenner MK (2017) Immunotherapy against cancer-related viruses. Cell Res 27(1):59–73
Trivedi B (2012) Microbiome: the surface brigade. Nature 492(7429):S60–S61
Tsilimigras MC, Fodor A, Jobin C (2017) Carcinogenesis and therapeutics: the microbiota perspective. Nat Microbiol 2:17008
Turnbaugh PJ, Gordon JI (2009) The core gut microbiome, energy balance and obesity. J Physiol 587(Pt 17):4153–4158
Turnbaugh PJ et al (2007) The human microbiome project. Nature 449(7164):804–810
Uribe-Herranz M et al (2018) Gut microbiota modulates adoptive cell therapy via CD8alpha dendritic cells and IL-12. JCI Insight 3(4). pii: 94952. PMID: 29467322
Valdimarsson H et al (2009) Psoriasis – as an autoimmune disease caused by molecular mimicry. Trends Immunol 30(10):494–501
van Nood E, Dijkgraaf MG, Keller JJ (2013) Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med 368(22):2145
Venter JC et al (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304(5667):66–74
Vetizou M et al (2015) Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350(6264):1079–1084
Wade W (2002) Unculturable bacteria – the uncharacterized organisms that cause oral infections. J R Soc Med 95(2):81–83
Warren RL et al (2013) Co-occurrence of anaerobic bacteria in colorectal carcinomas. Microbiome 1(1):16
Welton JC, Marr JS, Friedman SM (1979) Association between hepatobiliary cancer and typhoid carrier state. Lancet 1(8120):791–794
Wong WF, Santiago M (2017) Microbial approaches for targeting antibiotic-resistant bacteria. Microb Biotechnol 10(5):1047–1053
Wu S et al (2009) A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15(9):1016–1022
Yang Y, Jobin C (2017) Novel insights into microbiome in colitis and colorectal cancer. Curr Opin Gastroenterol 33(6):422–427
Yi M et al (2018) Gut microbiome modulates efficacy of immune checkpoint inhibitors. J Hematol Oncol 11(1):47
Yoshimoto S et al (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499(7456):97–101
Yu J et al (2016) Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway. Int J Cancer 139(6):1318–1326
Zhang J et al (2018) Evaluation of different 16S rRNA gene V regions for exploring bacterial diversity in a eutrophic freshwater lake. Sci Total Environ 618:1254–1267
Zitvogel L et al (2015) Cancer and the gut microbiota: an unexpected link. Sci Transl Med 7(271):271ps1
Zitvogel L et al (2017) Anticancer effects of the microbiome and its products. Nat Rev Microbiol 15(8):465–478
Zitvogel L et al (2018) The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science 359(6382):1366–1370
Zmora N et al (2018) Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174(6):1388–1405.e21
Zou S, Fang L, Lee MH (2018) Dysbiosis of gut microbiota in promoting the development of colorectal cancer. Gastroenterol Rep (Oxf) 6(1):1–12
Zuo T et al (2018) Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection. Nat Commun 9(1):3663
Author Contributions
Conception: Hermann and Wargo
Writing: Arora and Wargo
Creation of figures: Arora and Wargo
Critical review and revision of the manuscript: All authors
Conflict of Interest Disclosures
J. Wargo is an inventor on a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center that covers methods to enhance immune checkpoint blockade responses by modulating the microbiome. J. Wargo is a paid speaker for Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune, and Bristol-Myers Squibb. She is a consultant/advisory board member for Roche-Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, and MicrobiomeDx. J. Wargo also receives clinical trial support from GlaxoSmithKline, Roche-Genentech, Bristol-Myers Squibb, and Novartis. J. Wargo is a clinical and scientific advisor at MicrobiomeDx and a consultant at Biothera Pharma and Merck Sharp and Dohme.
The other authors declared no conflicts of interest.
Funding/Support
J. Wargo has honoraria from speakers’ bureau of Dava Oncology, Bristol-Myers Squibb, and Illumina and is an advisory board member for GlaxoSmithKline, Novartis, and Roche-Genentech. J. Wargo is supported by the NIH (1 R01 CA219896-01A1), US-Israel Binational Science Foundation (201332), Kennedy Memorial Foundation (0727030), the Melanoma Research Alliance (4022024), American Association for Cancer Research Stand Up To Cancer (SU2C-AACR-IRG-19-17), Department of Defense (W81XWH-16-1-0121), MD Anderson Cancer Center Multidisciplinary Research Program Grant, Andrew Sabin Family Fellows Program, and MD Anderson Cancer Center’s Melanoma Moon Shots Program. J. Wargo is a member of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this entry
Cite this entry
Arora, R., Hermann, A., Wargo, J.A. (2019). Microbiome and Melanoma. In: Fisher, D., Bastian, B. (eds) Melanoma. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7322-0_41-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7322-0_41-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-7322-0
Online ISBN: 978-1-4614-7322-0
eBook Packages: Springer Reference MedicineReference Module Medicine