Science – Seerave

Rationale

Evidence

Conviction

It is our conviction that more benign approaches can be developed to treat cancers and other illnesses by modulating the nutrition / microbiome / metabolite / immune system axis. New technologies have the potential to measure the impact of these approaches. Our conviction has evolved from:

Rigorous analysis of existing
peer-reviewed research from
credible high-impact journals.

Observations of a gap between
current clinical practice and
many promising novel approaches.

Observations made from impact
of lifestyle changes when
dealing with the disease of Eva Rees.

Scientific rationale

for the nutrition / microbiome / metabolite / immune system axis

Humans have evolved to live in symbiosis with microbes – bacteria, archea, viruses, fungi and protozoa.
More than 99% of these microbes are bacteria (ca: 100 trillion) living within the human gut (the “gut microbiome”).
Ten times as many bacteria inhabit a human body as there are cells in that body, and the vast majority of these bacteria are helpful and sometimes necessary for human survival.
Numerous nutrients are metabolized by the gut microbiome which in turn determines the extent these nutrients and/or their metabolites are taken up by the host.
The resulting metabolites (collectively called the “gut metabolome”) can have potent effects on human physiology, including the brain, metabolism and immune cell function.
Efficient immune cell function is needed to kill or keep cancer cells at bay. Regulation of immune cells with immunotherapy (e.g. checkpoint blockade) has emerged as one of the most promising approaches to anti-cancer therapy.
Given the interplay between the microbiome and the immune system, and in turn the immune system and cancer, there is an increasing body of scientific evidence showing that a poorly functioning gut microbiome negatively impacts immune cells and in turn allows cancer development.
In contrast a healthy microbiome has been shown to increase the efficacy of cancer immunotherapy (only 20-30% of patients usually respond to current treatments) and reduce the side effects of immunotherapy drugs.

Evidence

Our goal is to work with partners, establishing scientific proof of principle and ultimately clinical proof of principle that novel benign approaches to cancer are safe and efficacious and may also complement current therapies. Our aim is for partners to publish this evidence when these foundation supported projects are completed.

So far from our research and discussions with experts, we have identified some key peer-reviewed publications and sources which underpin our rationale that more benign approaches can be developed to treat cancers and other illnesses by modulating the nutrition/microbiome/metabolite/immune system axis. It is interesting to observe that there is quite a range of published research on different elements of this axis (see below). Our goal at Seerave is to join the dots between these different elements and the diverse research efforts.

Please note that we do not necessarily endorse any of the peer-reviewed publications.

1 .Nutrition / Microbiome

2019

An Apple a Day: Which Bacteria Do We Eat With Organic and Conventional Apples?

Frontiers in Microbiology (2019). Wassermann, B., Müller, H., & Berg, G.

http://doi.org/10.3389/fmicb.2019.01629

Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial.

Gut (2019). Wan, Y., Wang, F., Yuan, J., Li, J., Jiang, D., Zhang, J., et al.

http://doi.org/10.1136/gutjnl-2018-317609

Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers.

mBio (2019). Baxter, N. T., Schmidt, A. W., Venkataraman, A., Kim, K. S., Waldron, C., & Schmidt, T. M.

http://doi.org/10.1128/mBio.02566-18

Dietary emulsifiers consumption alters anxiety-like and social- related behaviors in mice in a sex-dependent manner.

Scientific Reports (2019). Holder, M. K., Peters, N. V., Whylings, J., Fields, C. T., Gewirtz, A. T., Chassaing, B., & de Vries, G. J.

http://doi.org/10.1038/s41598-018-36890-3

Trial watch: dietary interventions for cancer therapy.

Oncoimmunology (2019). Lévesque, S., Pol, J. G., Ferrere, G., Galluzzi, L., Zitvogel, L., & Kroemer, G.

http://doi.org/10.1080/2162402X.2019.1591878

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice.

Oncoimmunology (2019). Lévesque, S., Le Naour, J., Pietrocola, F., Paillet, J., Kremer, M., Castoldi, F., et al. (2019).

http://doi.org/10.1080/2162402X.2019.1657375

2018

Walnut Consumption Alters the Gastrointestinal Microbiota, Microbially Derived Secondary Bile Acids, and Health Markers in Healthy Adults: A Randomized Controlled Trial.

The Journal of Nutrition (2018). Holscher, H. D., Guetterman, H. M., Swanson, K. S., An, R., Matthan, N. R., Lichtenstein, A. H., et al.

http://doi.org/10.1093/jn/nxy004

Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.

Science (2018). Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y. Y., Wang, X., et al.

http://doi.org/10.1126/science.aao5774

Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies.

Nature Microbiology (2018). Tramontano, M., Andrejev, S., Pruteanu, M., Klünemann, M., Kuhn, M., Galardini, M., et al.

http://doi.org/10.1038/s41564-018-0123-9

Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model.

Nature Microbiology (2018). Hryckowian, A. J., Treuren, W., Smits, S. A., Davis, N. M., Gardner, J. O., Bouley, D. M., & Sonnenburg, J. L.

http://doi.org/10.1038/s41564-018-0150-6

Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention.

Nature Biomedical Engineering (2018). Ho, C. L., Tan, H. Q., Chua, K. J., Kang, A., Lim, K. H., Ling, K. L., et al.

http://doi.org/10.1038/s41551-017-0181-y

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health.

Cell Host and Microbe (2018). Zou, J., Chassaing, B., Singh, V., Pellizzon, M., Ricci, M., Fythe, M. D., et al.

http://doi.org/10.1016/j.chom.2017.11.003

Commensals Suppress Intestinal Epithelial Cell Retinoic Acid Synthesis to Regulate Interleukin-22 Activity and Prevent Microbial Dysbiosis.

Immunity (2018). Grizotte-Lake, M., Zhong, G., Duncan, K., Kirkwood, J., Iyer, N., Smolenski, I., et al. http://doi.org/10.1016/j.immuni.2018.11.018

2017

Nutrition, inflammation and cancer.

Nature Immunology (2017). Zitvogel, L., Pietrocola, F., & Kroemer, G.

http://doi.org/10.1038/ni.3754

Bread Affects Clinical Parameters and Induces Gut Microbiome - Associated Personal Glycemic Responses.

Cell Metabolism (2017). Korem, T., Zeevi, D., Zmora, N., Weissbrod, O., Bar, N., Lotan-Pompan, M., et al.

http://doi.org/10.1016/j.cmet.2017.05.002

Could food act as personalized medicine for chronic disease?

Personalized Medicine (2017). Toribio-Mateas, M. A., & Spector, T. D.

http://doi.org/10.2217/pme-2016-0017

Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans.

Cell (2017). Scott, T. A., Quintaneiro, L. M., Norvaisas, P., Lui, P. P., Wilson, M. P., Leung, K.-Y., et al.

http://doi.org/10.1016/j.cell.2017.03.040

Prebiotic inulin-type fructans induce specific changes in the human gut microbiota.

Gut (2017). Vandeputte, D., Falony, G., Vieira-Silva, S., Wang, J., Sailer, M., Theis, S., et al.

http://doi.org/10.1136/gutjnl-2016-313271

Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome.

mBio (2017). Maier, T. V., Lucio, M., Lee, L. H., VerBerkmoes, N. C., Brislawn, C. J., Bernhardt, J., et al.

http://doi.org/10.1128/mBio.01343-17

Interactions Between Diet and the Intestinal Microbiota Alter Intestinal Permeability and Colitis Severity in Mice.

Gastroenterology (2017). Llewellyn, S. R., Britton, G. J., Contijoch, E. J., Vennaro, O. H., Mortha, A., Colombel, J.-F., et al.

http://doi.org/10.1053/j.gastro.2017.11.030

Salt-responsive gut commensal modulates TH17 axis and disease.

Nature (2017). Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., et al.

http://doi.org/10.1038/nature24628

Functional properties of anti-inflammatory substances from quercetin-treated Bifidobacterium adolescentis.

Bioscience, Biotechnology, and Biochemistry (2017). Kawabata, K., Baba, N., Sakano, T., Hamano, Y., Taira, S., Tamura, A., et al.

http://doi.org/10.1080/09168451.2017.1401916

Influence of diet on the gut microbiome and implications for human health.

Journal of Translational Medicine (2017). Singh, R. K., Chang, H.-W., Di Yan, Lee, K. M., Ucmak, D., Wong, K., et al.

http://doi.org/10.1186/s12967-017-1175-y

2016

Food: a new form of personalised (gut microbiome) medicine for chronic diseases?

Journal of the Royal Society of Medicine (2016). Pallister, T., & Spector, T. D.

http://doi.org/10.1177/0141076816658786

Diet–microbiota interactions as moderators of human metabolism.

Nature (2016). Sonnenburg, J. L., & Bäckhed, F.

http://doi.org/10.1038/nature18846

From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

Cell (2016). Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F.

http://doi.org/10.1016/j.cell.2016.05.041

Taking it Personally: Personalized Utilization of the Human Microbiome in Health and Disease.

Cell Host and Microbe (2016). Zmora, N., Zeevi, D., Korem, T., Segal, E., & Elinav, E.

http://doi.org/10.1016/j.chom.2015.12.016

2015

Personalized Nutrition by Prediction of Glycemic Responses.

Cell (2015). Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., et al.

http://doi.org/10.1016/j.cell.2015.11.001

Fat, fibre and cancer risk in African Americans and rural Africans.

Nature (2015). O’Keefe, S., Li, J. V., Lahti, L., Ou, J., & Carbonero, F.

http://doi.org/10.1038/ncomms7342

Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children.

Ebiom (2015). Zhang, C., Yin, A., Li, H., Wang, R., Wu, G., Shen, J., et al.

http://doi.org/10.1016/j.ebiom.2015.07.007

2014

Nutritional modulation of the metabonome.

Current Opinion in Gastroenterology (2014). Kinross, J., Li, J. V., Muirhead, L. J., & Nicholson, J.

http://doi.org/10.1097/MOG.0000000000000036

2013

Diet rapidly and reproducibly alters the human gut microbiome.

Nature (2013). David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., et al. (2013)., 1–18.

http://doi.org/10.1038/nature12820

The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.

http://doi.org/10.1126/science.1241165

The abundance and variety of carbohydrate-active enzymes in the human gut microbiota.

Nature Reviews Cancer (2013). Kaoutari, El, A., Armougom, F., Gordon, J. I., Raoult, D., & Henrissat, B.

http://doi.org/10.1038/nrmicro3050

2 .Microbiome / Metabolites / Immune system

2019

A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology.

Cell (2019). Chen, H., Nwe, P.-K., Yang, Y., Rosen, C. E., Bielecka, A. A., Kuchroo, M., et al.

http://doi.org/10.1016/j.cell.2019.03.036

The intestinal microbiota fuelling metabolic inflammation.

Nat Rev Immunol (2019). Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E.

http://doi.org/10.1038/s41577-019-0198-4

T cell-mediated regulation of the microbiota protects against obesity.

Science (2019). Petersen, C., Bell, R., Klag, K. A., Lee, S.-H., Soto, R., Ghazaryan, A., et al.

http://doi.org/10.1126/science.aat9351

Microbial Contribution to the Human Metabolome: Implications for Health and Disease.

Annual Review of Pathology (2019). Van Treuren, W., & Dodd, D.

http://doi.org/10.1146/annurev-pathol-020117-043559

Blood metabolome predicts gut microbiome α-diversity in humans.

Nature Biotechnology (2019). Wilmanski, T., Rappaport, N., Earls, J. C., Magis, A. T., Manor, O., Lovejoy, J., et al. http://doi.org/10.1038/s41587-019-0233-9

2018

Immune regulation by microbiome metabolites.

Kim, C. H.

http://doi.org/10.1111/imm.12930

A common antimicrobial additive increases colonic inflammation and colitis-associated colon tumorigenesis in mice.

Science Translational Medicine (2018). Yang, H., Wang, W., Romano, K. A., Gu, M., Sanidad, K. Z., Kim, D., et al.

http://doi.org/10.1126/scitranslmed.aan4116

Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease.

Cell Host and Microbe (2018). Agus, A., Planchais, J., & Sokol, H.

http://doi.org/10.1016/j.chom.2018.05.003

2017

Commensal bacteria make GPCR ligands that mimic human signalling molecules.

Nature (2017). Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., et al.

http://doi.org/10.1038/nature23874

Lactobacillus reuteri induces gut intraepithelial CD4+CD8+ T cells.

Science (2017). Cervantes-Barragan, L., Chai, J. N., Tianero, M. D., Di Luccia, B., Ahern, P. P., Merriman, J., et al.

http://doi.org/10.1126/science.aah5825

A randomized synbiotic trial to prevent sepsis among infants in rural India.

Nature (2017). Panigrahi, P., Parida, S., Nanda, N. C., Satpathy, R., Pradhan, L., Chandel, D. S., et al.

http://doi.org/10.1038/nature23480

Regulation of inflammation by microbiota interactions with the host.

Nature Immunology (2017). Blander, J. M., Longman, R. S., Iliev, I. D., Sonnenberg, G. F., & Artis, D.

http://doi.org/10.1038/ni.3780

Homeostatic Immunity and the Microbiota.

Immunity (2017). Belkaid, Y., & Harrison, O. J.

http://doi.org/10.1016/j.immuni.2017.04.008

Microbe Hunting Hits Home.

Cell Host and Microbe (2017). Ivanov, I. I.

http://doi.org/10.1016/j.chom.2017.02.010

An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk.

Cell (2017). Yissachar, N., Zhou, Y., Ung, L., Lai, N. Y., Mohan, J. F., Ehrlicher, A., et al.

http://doi.org/10.1016/j.cell.2017.02.009

Mining the Human Gut Microbiota for Immunomodulatory Organisms.

Cell (2017). Geva-Zatorsky, N., Sefik, E., Kua, L., Pasman, L., Tan, T. G., Ortiz-Lopez, A., et al.

http://doi.org/10.1016/j.cell.2017.01.022

Microbiome, metabolites and host immunity.

Current Opinion in Microbiology (2017). Levy, M., Blacher, E., & Elinav, E.

http://doi.org/10.1016/j.mib.2016.10.003

Deciphering interactions between the gut microbiota and the immune system via microbial cultivation and minimal microbiomes.

Immunol Rev (2017). Clavel, T., Gomes-Neto, J. C., Lagkouvardos, I., & Ramer-Tait, A. E.

http://doi.org/10.1111/imr.12578

A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites.

Nature (2017). Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., et al.

http://doi.org/10.1038/nature24661

2016

Cellular Organization of Neuroimmune Interactions in the Gastrointestinal Tract.

Trends in Immunology (2016). Margolis, K. G., Gershon, M. D., & Bogunovic, M.

http://doi.org/10.1016/j.it.2016.05.003

How colonization by microbiota in early life shapes the immune system.

Science (2016). Gensollen, T., Iyer, S. S., Kasper, D. L., & Blumberg, R. S.

http://doi.org/10.1126/science.aad9378

Signals from the gut microbiota to distant organs in physiology and disease.

Schroeder, B. O., & Bäckhed, F.

http://doi.org/10.1038/nm.4185

CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands.

Nature Medicine (2016). Lamas, B., Richard, M. L., Leducq, V., Pham, H.-P., Michel, M.-L., Da Costa, G., et al.

http://doi.org/10.1038/nm.4102

2015

Commensal-dendritic-cell interaction specifies a unique protective skin immune signature.

Nature (2015). Naik, S., Bouladoux, N., Linehan, J. L., Han, S.-J., Harrison, O. J., Wilhelm, C., et al.

http://doi.org/10.1038/nature14052

Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences.

Cell (2015). Brodin, P., Jojic, V., Gao, T., Bhattacharya, S., Angel, C. J. L., Furman, D., et al. (2015).

http://doi.org/10.1016/j.cell.2014.12.020

2014

The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition.

Proceedings of the National Academy of Sciences (2014). Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R.

http://doi.org/10.1073/pnas.1322269111

Sphingolipids from a Symbiotic Microbe Regulate Homeostasis of Host Intestinal Natural Killer T Cells.

Cell (2014). An, D., Oh, S. F., Olszak, T., Neves, J. F., Avci, F. Y., Erturk-Hasdemir, D., et al.

http://doi.org/10.1016/j.cell.2013.11.042

2013

Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.

Nature (2013). Arpaia, N., Campbell, C., Fan, X., Dikiy, S., van der Veeken, J., deRoos, P., et al. (2013).

http://doi.org/10.1038/nature12726

The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

Science (2013). Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., et al.

http://doi.org/10.1126/science.1241165

Compartmentalized and systemic control of tissue immunity by commensals.

Nature Immunology (2013). Belkaid, Y., & Naik, S.

http://doi.org/10.1038/ni.2604

Tryptophan Catabolites from Microbiota Engage Aryl Hydrocarbon Receptor and Balance Mucosal Reactivity via Interleukin-22.

Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., et al.

http://doi.org/10.1016/j.immuni.2013.08.003

2005

An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

Cell (2005). Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005).

http://doi.org/10.1016/j.cell.2005.05.007

3 .Immune system / Cancer

2019

Transposable element expression in tumors is associated with immune infiltration and increased antigenicity.

Nature Communications (2019). Kong, Y., Rose, C. M., Cass, A. A., Williams, A. G., Darwish, M., Lianoglou, S., et al.

http://doi.org/10.1038/s41467-019-13035-2

MHC-II neoantigens shape tumour immunity and response to immunotherapy.

Nature (2019). Alspach, E., Lussier, D. M., Miceli, A. P., Kizhvatov, I., DuPage, M., Luoma, A. M., et al. (2019). 574(7780), 696–701.

http://doi.org/10.1038/s41586-019-1671-8

Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade.

Cell Research (2019). Jacquelot, N., Yamazaki, T., Roberti, M. P., Duong, C. P. M., Andrews, M. C., Verlingue, L., et al.

http://doi.org/10.1038/s41422-019-0224-x

Defining “T cell exhaustion.”

Nat Rev Immunol (2019). Blank, C. U., Haining, W. N., Held, W., Hogan, P. G., Kallies, A., Lugli, E., et al.

http://doi.org/10.1038/s41577-019-0221-9

Multiomics Prediction of Response Rates to Therapies to Inhibit Programmed Cell Death 1 and Programmed Cell Death 1 Ligand 1.

JAMA Oncology (2019). Lee, J. S., & Ruppin, E. (2019). http://doi.org/10.1001/jamaoncol.2019.2311

Metabolic landscape of the tumor microenvironment at single cell resolution.

Nature Communications (2019). Xiao, Z., Dai, Z., & Locasale, J. W. (2019). 1–12.

http://doi.org/10.1038/s41467-019-11738-0

Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.

Lancet Oncology (2019). MD, E. A. R., MD, A. M. M., van Akkooi MD, A. C. J., MD, C. A., BSc, C. B., van de Wiel MD, B. A., et al.

http://doi.org/10.1016/S1470-2045(19)30151-2

Adaptive Immune Resistance Emerges from Tumor-Initiating Stem Cells.

Cell (2019). Miao, Y., Yang, H., Levorse, J., Yuan, S., Polak, L., Sribour, M., et al.

http://doi.org/10.1016/j.cell.2019.03.025

Approaches to treat immune hot, altered and cold tumours with combination immunotherapies.

Nature Reviews Drug Discovery (2019). Galon, J., & Bruni, D.

http://doi.org/10.1038/s41573-018-0007-y

The Dendritic Cell Strikes Back.

Immunity (2019). Moussion, C., & Mellman, I. http://doi.org/10.1016/j.immuni.2019.01.022

Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma.

Cell (2019). Li, H., van der Leun, A. M., Yofe, I., Lubling, Y., Gelbard-Solodkin, D., van Akkooi, A. C. J., et al.

http://doi.org/10.1016/j.cell.2018.11.043

Tumor mutational load predicts survival after immunotherapy across multiple cancer types.

Nature Genetics (2019). Samstein, R. M., Lee, C.-H., Shoushtari, A. N., Hellmann, M. D., Shen, R., Janjigian, Y. Y., et al.

http://doi.org/10.1038/s41588-018-0312-8

What, Why, Where, and When: Bringing Timing to Immuno-Oncology.

Trends Immunol (2019). Rothschilds, A. M., & Wittrup, K. D.

http://doi.org/10.1016/j.it.2018.11.003

Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

Nature Medicine (2019). Scheper, W., Kelderman, S., Fanchi, L. F., Linnemann, C., Bendle, G., de Rooij, M. A. J., et al. http://doi.org/10.1038/s41591-018-0266-5

2018

Tumor immune evasion arises through loss of TNF sensitivity.

Kearney, C. J., Vervoort, S. J., Hogg, S. J., Ramsbottom, K. M., Freeman, A. J., Lalaoui, N., et al. (2018).

http://doi.org/10.1126/sciimmunol.aar3451

Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis.

Lancet Oncology (2018). MD, F. C., MD, L. P., PhD, V. B., De Pas MD, T., BSc, M. M., MD, P. G. V., et al.

http://doi.org/10.1016/S1470-2045(18)30261-4

Understanding the tumor immune microenvironment (TIME) for effective therapy.

Nature Medicine (2018). Binnewies, M., Roberts, E. W., Kersten, K., Chan, V., Fearon, D. F., Merad, M., et al.

http://doi.org/10.1038/s41591-018-0014-x

The Immune Landscape of Cancer.

Immunity (2018). Thorsson, V., Gibbs, D. L., Brown, S. D., Wolf, D., Bortone, D. S., Yang, T.-H. O., et al.

http://doi.org/10.1016/j.immuni.2018.03.023

2017

Predictors of responses to immune checkpoint blockade in advanced melanoma.

Nature (2017). Jacquelot, N., Roberti, M. P., Enot, D. P., Rusakiewicz, S., Ternès, N., Jegou, S., et al.

http://doi.org/10.1038/s41467-017-00608-2

Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma.

Science Translational Medicine (2017). Fankhauser, M., Broggi, M. A. S., Potin, L., Bordry, N., Jeanbart, L., Lund, A. W., et al.

http://doi.org/10.1126/scitranslmed.aal4712

Identification of CMTM6 and CMTM4 as PD-L1 protein regulators.

Nature (2017). Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., et al.

http://doi.org/10.1038/nature23669

An immunogenic personal neoantigen vaccine for patients with melanoma.

Nature (2017). Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., et al. (2017).

http://doi.org/10.1038/nature22991

Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells.

Nature Communications (2017). Enamorado, M., Iborra, S., Priego, E., Cueto, F. J., Quintana, J. A., nez-Cano, S. M. I., et al.

http://doi.org/10.1038/ncomms16073

Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy.

Nature Reviews Immunology (2017). Nagarsheth, N., Wicha, M. S., & Zou, W.

http://doi.org/10.1038/nri.2017.49

Survival of patients with advanced metastatic melanoma: the impact of novel therapies-update.

European Journal of Cancer (2017). Ugurel, S., Röhmel, J., Ascierto, P. A., Flaherty, K. T., Grob, J. J., Hauschild, A., et al.

http://doi.org/10.1016/j.ejca.2017.06.028

2016

Dendritic Cells and Cancer Immunity.

Trends in Immunology (2016). Gardner, A., & Ruffell, B.

http://doi.org/10.1016/j.it.2016.09.006

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Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

Cell (2016). Hugo, W., Zaretsky, J. M., Sun, L., Song, C., Moreno, B. H., Hu-Lieskovan, S., et al.

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The tumor microenvironment and immunoscore are critical determinants of dissemination to distant metastasis.

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The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment.

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NK cells and cancer: you can teach innate cells new tricks.

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Lymphatic vessels, inflammation, and immunity in skin cancer.

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Immune suppressive mechanisms in the tumor microenvironment.

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Acquired resistance to immunotherapy and future challenges.

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2015

Adaptive Immune Resistance: How Cancer Protects from Immune Attack.

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The Next Hurdle in Cancer Immunotherapy: Overcoming the Non-T-Cell-Inflamed Tumor Microenvironment.

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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma.

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Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma.

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Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity.

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Neoantigens in cancer immunotherapy.

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Biomarkers in Cancer Immunotherapy.

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2011

Microbial Induction of Immunity, Inflammation, and Cancer.

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4 .Microbiome / Cancer

2019

Association of Prior Antibiotic Treatment With Survival and Response to Immune Checkpoint Inhibitor Therapy in Patients With Cancer.

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The cancer microbiome.

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Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Cell (2019). Riquelme, E., Zhang, Y., Zhang, L., Montiel, M., Zoltan, M., Dong, W., et al.

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Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5-/- mice.

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Commensal Microbiota Promote Lung Cancer Development via gamma delta T Cells.

Cell (2019) Jin, C., Lagoudas, G. K., Zhao, C., Bullman, S., Bhutkar, A., Hu, B., et al.

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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity.

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Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor–Positive Breast Cancer.

Cancer Research (2019). Buchta Rosean, C., Bostic, R. R., Ferey, J. C. M., Feng, T.-Y., Azar, F. N., Tung, K. S., et al.

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2018

Gut microbiome modulates efficacy of immune checkpoint inhibitors.

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The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies.

Zitvogel, L., Ma, Y., Raoult, D., Kroemer, G., & Gajewski, T. F.

http://doi.org/10.1126/science.aar6918

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.

Uribe-Herranz, M., Bittinger, K., Rafail, S., Guedan, S., Pierini, S., Tanes, C., et al.

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Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria.

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http://doi.org/10.1126/science.aah3648

T cell cross-reactivity may explain the large variation in how patients respond to checkpoint inhibitors.

Scand J Immunol (2018). Sioud, M.

http://doi.org/10.1111/sji.12643

The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.

Science (2018). Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M.-L., et al.

http://doi.org/10.1126/science.aao3290

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.

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Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression.

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2017

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors.

Science (2017). Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., et al. (2017).

http://doi.org/10.1126/science.aan3706

Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients.

Science (2017). Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., et al.

http://doi.org/10.1126/science.aan4236

Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients.

Neoplasia (2017). Frankel, A. E., Coughlin, L. A., Kim, J., Froehlich, T. W., Xie, Y., Frenkel, E. P., & Koh, A. Y.

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The microbiome and the hallmarks of cancer.

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Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine.

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Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy.

Cell (2017). Yu, T., Guo, F., Yu, Y., Sun, T., Ma, D., Han, J., et al.

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Anticancer effects of the microbiome and its products.

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http://doi.org/10.1038/nrmicro.2017.44

The microbiome in anti-cancer therapy.

Semin Immunol (2017). Bashiardes, S., Tuganbaev, T., Federici, S., & Elinav, E.

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Microbiota: a key orchestrator of cancer therapy.

Nature Reviews Cancer (2017). Roy, S., & Trinchieri, G.

http://doi.org/10.1038/nrc.2017.13

Carcinogenesis and therapeutics: the microbiota perspective.

Nature Reviews Cancer (2017). Tsilimigras, M. C. B., Fodor, A., & Jobin, C.

http://doi.org/10.1038/nmicrobiol.2017.8

Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer.

Bullman, S., Pedamallu, C. S., Sicinska, E., Clancy, T. E., Zhang, X., Cai, D., et al.

http://doi.org/10.1126/science.aal5240

Oral Microbiome Composition Reflects Prospective Risk for Esophageal Cancers.

Peters, B. A., Wu, J., Pei, Z., Yang, L., Purdue, M. P., Freedman, N. D., et al.

http://doi.org/10.1158/0008-5472.CAN-17-1296

2016

Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects.

Immunity (2016). Daillère, R., Vétizou, M., Waldschmitt, N., Yamazaki, T., Isnard, C., Poirier-Colame, V., et al.

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