Elsevier

Seminars in Cancer Biology

Volume 46, October 2017, Pages 182-190
Seminars in Cancer Biology

Review article
Probiotic species in the modulation of the anticancer immune response

https://doi.org/10.1016/j.semcancer.2017.08.007 Get rights and content

Abstract

Mounting evidences are supporting a key role of distinct gut bacteria in the occurrence and progression of intestinal and extra-intestinal tumors. More importantly, it has been recently demonstrated that some gut bacteria strains synergize with largely-used anticancer drugs as alkylating or immune checkpoint blockade agents thus optimizing the immune response against multiple solid cancers. However, the exact role played by each gut bacterium in cancer occurrence and response to therapy is still in its infancy; and the current knowledge, although exciting, still needs to be transferred from mice models to human beings. Here, the advances in the understanding of how gut microbes and immune response shape each other in a cancer context are reviewed together with the implications of these finding for future antitumor therapy. Herein, the most important bacteria strains, able to boost the immune response triggered by anticancer drugs, together with their mechanism of action, whenever known, have been surveyed. It is reasonable to think that cocktails of beneficial bacteria together with an ad hoc diet or food supplements may be used as novel anticancer adjuvant agents in future therapeutic regimens.

Section snippets

The mammalian immune system and cancer

Cancer arises from the accumulation of a variable number of genetic alterations that reroute key pathways in the regulation of cell survival and death. In principle, adaptive immunity should be able to prevent cancer development, at least in immune-competent hosts [1]. However, for an effective anticancer immune response, a series of events has to be initiated and allowed to proceed and expand iteratively [2].

At first, tumor antigens originated from different sources, such as mutations

The gut microbiota in immune homeostasis and cancer

Human intestine harbors hundred trillion organisms (mainly bacteria), representing the most densely populated ecosystem known to date [21]. The bacterial, fungal, and viral intestinal communities are commonly referred to as the gut microbiota and altogether their genomes are referred to as the gut microbiome. In humans, the latter may encode ∼150 times more genes than human genomes themselves, thus the gut microenvironment may be regarded as a complex bioreactor replete with diverse biochemical

Probiotic bacteria strains reprogram anticancer immune response

The most significant in vitro, in vivo, and clinical studies, regarding the influence of probiotic bacteria strains on anticancer immune response are indicated in Table 1.

Novel perspectives: manipulation of gut microbiota through probiotics to mount immunotherapy efficacy in cancer patients

The fact that the gut microbiota has a substantial influence on immune responses, in animals as well as in humans, has been now extensively demonstrated [23], [67], [111]. However, recently, mounting evidences suggest that an “optimal” microbiota can efficiently optimize the immune response against multiple solid cancers. More importantly, it has been demonstrated that some gut bacteria strains synergize with largely-used anticancer drugs as alkylating or immune checkpoint blockade agents. In

Concluding remarks

The recent flurry of scientific works on the effects of intestinal microbiota on tumors opens up an entirely new approach to the understanding and treatment of cancer disease. However, all the above-mentioned results have to be interpreted with caution as every experiment was made on cancers mice models. The next effort will be to apply all the acquired knowledge to human being and important differences may arise. It will be of fundamental importance to recognize exactly which bacteria strains

Conflict of interest

The authors declare that there are no conflicts of interest.

Funding

None.

Acknowledgement

The assistance of the staff is gratefully appreciated.

References (114)

  • Y.P. Rubtsov et al.

    Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces

    Immunity

    (2008)
  • S.G. Park et al.

    T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells

    Immunity

    (2010)
  • S. Huber et al.

    Th17 cells express interleukin-10 receptor and are controlled by Foxp3-and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner

    Immunity

    (2011)
  • C. Tang et al.

    Inhibition of Dectin-1 signaling ameliorates colitis by inducing Lactobacillus-mediated regulatory T cell expansion in the intestine

    Cell Host Microbe

    (2015)
  • H.M. Chen et al.

    Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma

    Am. J. Clin. Nutr.

    (2013)
  • D.H. Dapito et al.

    Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4

    Cancer Cell

    (2012)
  • R. Daillère et al.

    Enterococcus hirae and Barnesiella intestinihominis Facilitate cyclophosphamide-induced therapeutic immunomodulatory effects

    Immunity

    (2016)
  • F. Aragón et al.

    The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model

    Immunobiology

    (2014)
  • R.D. Schreiber et al.

    Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion

    Science

    (2011)
  • D.H. Raulet

    Interplay of natural killer cells and their receptors with the adaptive immune response

    Nat. Immunol.

    (2004)
  • M.A. Degli-Esposti et al.

    Close encounters of different kinds: dendritic cells and NK cells take centre stage

    Nat. Rev. Immunol.

    (2005)
  • F. Balkwill

    Tumour necrosis factor and cancer

    Nat. Rev. Cancer.

    (2009)
  • L. Corrales et al.

    Innate immune signaling and regulation in cancer immunotherapy

    Cell Res.

    (2017)
  • A. Tanaka et al.

    Regulatory T cells in cancer immunotherapy

    Cell Res.

    (2017)
  • W.H. Fridman et al.

    The immune contexture in human tumours: impact on clinical outcome

    Nat. Rev. Cancer

    (2012)
  • S. Farashi-bonab et al.

    Regulatory T Cells in cancer patients and their roles in cancer development/progression

    MOJ Immunol.

    (2014)
  • J.P. Allison et al.

    The Yin and Yang of T cell costimulation

    Science

    (1995)
  • T. Okazaki et al.

    A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application

    Nat. Immunol.

    (2013)
  • L.T. Nguyen et al.

    Clinical blockade of PD1 and LAG3 — potential mechanisms of action

    Nat. Rev. Immunol.

    (2015)
  • P. Sharma et al.

    The future of immune checkpoint therapy

    Science

    (2015)
  • M. McNutt

    Cancer immunotherapy

    Science

    (2013)
  • R. Kalluri

    The biology and function of fibroblasts in cancer

    Nat. Rev. Cancer

    (2016)
  • K.E. de Visser et al.

    Paradoxical roles of the immune system during cancer development

    Nat. Rev. Cancer

    (2006)
  • P.B. Eckburg et al.

    Diversity of the human intestinal microbial flora

    Science

    (2005)
  • J. Qin et al.

    A human gut microbial gene catalogue established by metagenomic sequencing

    Nature

    (2010)
  • C.L. Maynard et al.

    Reciprocal interactions of the intestinal microbiota and immune system

    Nature

    (2012)
  • Y.K. Lee et al.

    Has the microbiota played a critical role in the evolution of the adaptive immune system

    Science

    (2010)
  • R. Burcelin et al.

    Metagenome and metabolism: the tissue microbiota hypothesis

    Diabetes Obes. Metab.

    (2013)
  • L. Wen et al.

    Innate immunity and intestinal microbiota in the development of Type 1 diabetes

    Nature

    (2008)
  • M.G. Gareau et al.

    Probiotics and the gut microbiota in intestinal health and disease

    Nat. Rev. Gastroenterol. Hepatol.

    (2010)
  • W.M. de Vos et al.

    Role of the intestinal microbiome in health and disease:from correlation to causation

    Nutr. Rev.

    (2012)
  • K. Tsilingiri et al.

    Probiotic and postbiotic activity in health and disease: comparison on a novel polarised ex-vivo organ culture model

    Gut

    (2012)
  • E.P. Nyangale et al.

    Gut microbial activity, implications for health and disease: the potential role of metabolite analysis

    J. Proteome Res.

    (2012)
  • A.M. O'Hara et al.

    The gut flora as a forgotten organ

    EMBO Rep.

    (2006)
  • E.A. Eloe-Fadrosh et al.

    The human microbiome: from symbiosis to pathogenesis

    Annu. Rev. Med

    (2013)
  • I. Cho et al.

    The human microbiome: at the interface of health and disease

    Nat. Rev. Genet.

    (2012)
  • FAO et al.

    Evaluation of Health and Nutritional Properties of Powder Milk and Live Lactic Acid Bacteria

    (2001)
  • C.T. Peterson et al.

    Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota

    Clin. Exp. Immunol.

    (2015)
  • T.R. Klaenhammer et al.

    The impact of probiotics and prebiotics on the immune system

    Nat. Rev. Immunol.

    (2012)
  • N. Cerf-Bensussan et al.

    The immune system and the gut microbiota: friends or foes?

    Nat. Rev. Immunol.

    (2010)
  • Cited by (44)

    • Targeting emerging cancer hallmarks by transition metal complexes: Cancer stem cells and tumor microbiome. Part I

      2023, Coordination Chemistry Reviews
      Citation Excerpt :

      This manipulation can be achieved either through the activation of a favorable microbiome or inhibition of the unfavorable microbiome [329]. Administrating probiotics, a group of viable microorganisms which, in the right amounts, can confer health benefits, has been associated with the reduction of progression of various cancers [329,330]. For instance, the intravesical administration of L. casei to mice with bladder cancer resulted in a significantly reduced rate of tumor progression and increased infiltration of neutrophils and macrophages within the tumor microenvironment [331].

    • Probiotics and prebiotics in the prevention and management of human cancers (colon cancer, stomach cancer, breast cancer, and cervix cancer)

      2022, Probiotics in the Prevention and Management of Human Diseases: A Scientific Perspective
    • The pint- sized powerhouse: Illuminating the mighty role of the gut microbiome in improving the outcome of anti- cancer therapy

      2021, Seminars in Cancer Biology
      Citation Excerpt :

      That same year, a randomized clinical trial with CRC patients clearly underscored that administration of a mixture of pre- and probiotics can significantly lower post- operative infection rates in the patients [28]. Bifidobacterium is involved in the alteration of DC activity which augments the function of tumor- specific CD8 + T cells [94]. Administration of L. rhamnosus GG significantly participates in the reduced incidence of recurrent bladder cancer by enhancing the secretion of chemokine XCL1 from activated CD8+ and γδ T cells, NK and master cells [95].

    • Microbiome in cancer progression and therapy

      2020, Current Opinion in Microbiology
      Citation Excerpt :

      In contrast Germ free mice lack fully matured immune system and also depletion of microbiota with broad spectrum antibiotics can reduce the efficacy of immunosurveillance in mouse models [28]. This function is further extended to the ability of microbes to stimulate activation of various immune cells subsets; for example, members of Lactobacilla phylum activate antitumor immune responses by dendritic cell (DC) maturation [29] and subsequently for acquisition of cytotoxic properties by T cells, NK cells, NK T cells and anti-tumorigenic myeloid cells [30], while many types of bacteria can activate macrophages, neutrophils, DC and B cells. Fourth mechanism stems from the aforementioned ability of bacteria to drive activation of immune system and is related to the ability of some bacteria to improve anti-cancer therapies [6].

    View all citing articles on Scopus
    1

    These Authors contributed equally to this work.

    View full text