New Insights Into the Cancer–Microbiome–Immune Axis: Decrypting a Decade of Discoveries

Jain, Tejeshwar; Sharma, Prateek; Are, Abhi C.; Vickers, Selwyn M.; Dudeja, Vikas

doi:10.3389/fimmu.2021.622064

Cited by 106 publications

(107 citation statements)

References 260 publications

(348 reference statements)

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“…This was further supported when their response was restored upon being fed with Bacteroides fragilis (183). This has since been concluded in a number of studies that demonstrate that gut microbiome can affect a person's response to ICT treatment (184).…”

Section: Strategies To Overcome Resistance To Immune Checkpoint Blockade Therapymentioning

confidence: 86%

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy

et al. 2021

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Through genetic and epigenetic alterations, cancer cells present the immune system with a diversity of antigens or neoantigens, which the organism must distinguish from self. The immune system responds to neoantigens by activating naïve T cells, which mount an anticancer cytotoxic response. T cell activation begins when the T cell receptor (TCR) interacts with the antigen, which is displayed by the major histocompatibility complex (MHC) on antigen-presenting cells (APCs). Subsequently, accessory stimulatory or inhibitory molecules transduce a secondary signal in concert with the TCR/antigen mediated stimulus. These molecules serve to modulate the activation signal’s strength at the immune synapse. Therefore, the activation signal’s optimum amplitude is maintained by a balance between the costimulatory and inhibitory signals. This system comprises the so-called immune checkpoints such as the programmed cell death (PD-1) and Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and is crucial for the maintenance of self-tolerance. Cancers often evade the intrinsic anti-tumor activity present in normal physiology primarily by the downregulation of T cell activation. The blockade of the immune checkpoint inhibitors using specific monoclonal antibodies has emerged as a potentially powerful anticancer therapy strategy. Several drugs have been approved mainly for solid tumors. However, it has emerged that there are innate and acquired mechanisms by which resistance is developed against these therapies. Some of these are tumor-intrinsic mechanisms, while others are tumor-extrinsic whereby the microenvironment may have innate or acquired resistance to checkpoint inhibitors. This review article will examine mechanisms by which resistance is mounted against immune checkpoint inhibitors focussing on anti-CTL4-A and anti-PD-1/PD-Ll since drugs targeting these checkpoints are the most developed.

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Section: Strategies To Overcome Resistance To Immune Checkpoint Blockade Therapymentioning

confidence: 86%

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy

et al. 2021

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“…It is also noticed that factors promoting inflammation through different genetic defects affecting epithelial, myeloid, or lymphoid components of the intestinal immune system are carcinogenic through the induction of dysbiosis [ 39 ]. Thus, nowadays we know that tumor driver mutations can be regulated by the microbiota [ 40 ].…”

Section: Role Of Gut Microbiota In Cancer Development and Immunosurveillancementioning

confidence: 99%

“…Another mechanism through which microbiota can induce carcinogenesis is the induction of chronic inflammation. Inflammation plays an important part in the pathogenesis of cancer [ 40 ]. A chronic inflammatory state exists in multiple conditions, including inflammatory bowel disease, pancreatitis, and chronic atrophic gastritis, and was linked to the development of cancer through several mechanisms [ 41 ].…”

Section: Role Of Gut Microbiota In Cancer Development and Immunosurveillancementioning

confidence: 99%

“…A chronic inflammatory state exists in multiple conditions, including inflammatory bowel disease, pancreatitis, and chronic atrophic gastritis, and was linked to the development of cancer through several mechanisms [ 41 ]. In the same way, inflammation caused by microbes also favors carcinogenesis [ 40 ]. Examples include H. pylori as a causative agent of gastric cancer and Schistosoma haematobium infection as a risk factor for bladder cancer [ 40 ].…”

Section: Role Of Gut Microbiota In Cancer Development and Immunosurveillancementioning

confidence: 99%

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The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

Bouferraa

Chedid

Amhaz

et al. 2021

IJMS

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The introduction of immune checkpoint inhibitors has constituted a major revolution in the treatment of patients with cancer. In contrast with the traditional cytotoxic therapies that directly kill tumor cells, this treatment modality enhances the ability of the host’s immune system to recognize and target cancerous cells. While immune checkpoint inhibitors have been effective across multiple cancer types, overcoming resistance remains a key area of ongoing research. The gut microbiota and its role in cancer immunosurveillance have recently become a major field of study. Gut microbiota has been shown to have direct and systemic effects on cancer pathogenesis and hosts anti-tumor immune response. Many studies have also shown that the host microbiota profile plays an essential role in the response to immunotherapy, especially immune checkpoint inhibitors. As such, modulating this microbial environment has offered a potential path to overcome the resistance to immune checkpoint inhibitors. In this review, we will talk about the role of microbiota in cancer pathogenesis and immune-system activity. We will also discuss preclinical and clinical studies that have increased our understanding about the roles and the mechanisms through which microbiota influences the response to treatment with immune checkpoint inhibitors.

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“…Treating cancer patients with antibodies to inhibit immune checkpoint proteins represents the earliest immunotherapeutic cancer therapy. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor allows the T cells to kill tumor cells [ 37 ]. Growing evidence demonstrates the impact of gut microbiota on ICI efficacy.…”

Section: Gut Microbiota and Cancer Therapy: Bidirectional Interactionsmentioning

confidence: 99%

Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies

Rinninella

Raoul

Cintoni³

et al. 2021

Microorganisms

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The gut microbiome is increasingly being recognized for its influence on intestinal and extra-intestinal disorders such as cancer. Today, diet is the most studied environmental modulator of gut microbiota, capable of altering or improving it in terms of richness and diversity. Recent evidence from several preclinical and clinical trials suggested that gut microbiota composition could modulate cancer therapies (toxicities, treatment responses) and vice versa. This review highlights the latest research on the bidirectional associations between gut microbiota and cancer. We also dissect the role of gut microbiota during cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and functions. In this context, we summarize the state-of-the-art research regarding the role of various nutritional interventions—prebiotics, dietary strategies, and dietary restrictions—as cutting-edge possibilities to modulate gut microbiota during cancer therapies.

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New Insights Into the Cancer–Microbiome–Immune Axis: Decrypting a Decade of Discoveries

Cited by 106 publications

References 260 publications

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy

The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy

The Role of Gut Microbiota in Overcoming Resistance to Checkpoint Inhibitors in Cancer Patients: Mechanisms and Challenges

Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies

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