Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review

Chen, Minmin; Liu, Mengyuan; Li, Chenyan; Peng, Siyun; Li, Yiling; Xu, Xinglian; Sun, Mingjian; Sun, Xiaodi

doi:10.3389/fonc.2022.913217

Cited by 16 publications

(12 citation statements)

References 31 publications

(36 reference statements)

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“…The second patient had a decrease of all the T cell subtypes following FMT; however, the CD4 + T cell population was relatively unchanged compared to the CD8 + T cells, which was associated with the persistence of T reg cells in the colonic mucosa. In another recent case study ( 143 ), a patient suffering from palatal malignant melanoma developed severe ICI-associated colitis after the third dose of anti-PD-1 treatment. After unsuccessful treatment with corticosteroids, an FMT was administered to successfully resolve colitis symptoms.…”

Section: Section 5: Microbiome-based Therapies Acting On the Immune S...mentioning

confidence: 99%

“…After unsuccessful treatment with corticosteroids, an FMT was administered to successfully resolve colitis symptoms. The patient’s clinical outcome was associated with decreased fecal calprotectin and restoration of the congested, inflamed colonic mucosa to near normal level ( 143 ). These mucosal immune changes reported in the case reports suggest that FMT is signaling to reshape intestinal immune cell populations resulting in therapeutic effect against ICI-associated colitis.…”

Section: Section 5: Microbiome-based Therapies Acting On the Immune S...mentioning

confidence: 99%

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Immunological consequences of microbiome-based therapeutics

2023

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The complex network of microscopic organisms living on and within humans, collectively referred to as the microbiome, produce wide array of biologically active molecules that shape our health. Disruption of the microbiome is associated with susceptibility to a range of diseases such as cancer, diabetes, allergy, obesity, and infection. A new series of next-generation microbiome-based therapies are being developed to treat these diseases by transplanting bacteria or bacterial-derived byproducts into a diseased individual to reset the recipient’s microbiome and restore health. Microbiome transplantation therapy is still in its early stages of being a routine treatment option and, with a few notable exceptions, has had limited success in clinical trials. In this review, we highlight the successes and challenges of implementing these therapies to treat disease with a focus on interactions between the immune system and microbiome-based therapeutics. The immune activation status of the microbiome transplant recipient prior to transplantation has an important role in supporting bacterial engraftment. Following engraftment, microbiome transplant derived signals can modulate immune function to ameliorate disease. As novel microbiome-based therapeutics are developed, consideration of how the transplants will interact with the immune system will be a key factor in determining whether the microbiome-based transplant elicits its intended therapeutic effect.

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Section: Section 5: Microbiome-based Therapies Acting On the Immune S...mentioning

confidence: 99%

Section: Section 5: Microbiome-based Therapies Acting On the Immune S...mentioning

confidence: 99%

Immunological consequences of microbiome-based therapeutics

2023

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“…Convincing, if complex, association between the gut microbiome and cancer outcomes in CPI recipients has emerged ( 37 , 38 ). Moreover, case reports have demonstrated faecal microbiota transplant (FMT) can mitigate both anti-PD-1 tumour-resistance and treatment-refractory GI-irAEs ( 39 , 40 ), and antibiotic therapy is correlated with high-grade GI-irAE incidence ( 41 ) – all consistent with a critical immune-mediating role for the microbiome in this setting that has yet to be properly understood ( 42 ).…”

Section: Gastrointestinal Iraesmentioning

confidence: 99%

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

et al. 2023

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Checkpoint inhibitors (CPIs) are monoclonal antibodies which, by disrupting interactions of immune checkpoint molecules with their ligands, block regulatory immune signals otherwise exploited by cancers. Despite revolutionary clinical benefits, CPI use is associated with an array of immune-related adverse events (irAEs) that mirror spontaneous autoreactivity. Severe irAEs necessitate pausing or stopping of CPI therapy and use of corticosteroids and/or other immunomodulatory interventions. Despite increasingly widespread CPI use, irAE pathobiology remains poorly understood; its elucidation may point to targeted mitigation strategies and uncover predictive biomarkers for irAE onset in patients, whilst casting new light on mechanisms of spontaneous immune-mediated disease. This review focuses on common CPI-induced irAEs of the gut, skin and synovial joints, and how these compare to immune-mediated diseases such as ulcerative colitis, vitiligo and inflammatory arthritis. We review current understanding of the immunological changes reported following CPI therapy at the level of peripheral blood and tissue. Many studies highlight dysregulation of cytokines in irAE-affected tissue, particularly IFNγ and TNF. IrAE-affected tissues are also predominantly infiltrated by T-cells, with low B-cell infiltration. Whilst there is variability between studies, patients treated with anti-programmed cell death-1 (PD-1)/PDL-1 therapies seem to exhibit CD8+ T-cell dominance, with CD4+ T-cells dominating in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monotherapy. Interestingly, CD8+CXCR3+ T-cells have been reported to be elevated in gastrointestinal, dermatological and musculoskeletal -irAE affected tissues. These findings may highlight potential opportunities for therapeutic development or re-deployment of existing therapies to prevent and/or improve the outcome of irAEs.

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“…Similarly, the enormous potential of fecal microbiota transplantation (FMT) might be a promising therapeutic strategy to alter and/or repair the composition of gut microbiota [ 34 ]. It has been shown that FMT can effectively cure patients with IRAEs [ 35 ]. A favorable microbiota might have the potential to ameliorate IRAEs [ 36 ].…”

Section: How To Manage the Iraesmentioning

confidence: 99%

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma

Yoshikawa

Taniguchi

Sawamura

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

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Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an “engram theory” for the innovative treatment of IRAEs.

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Fecal Microbiota Transplantation Effectively Cures a Patient With Severe Bleeding Immune Checkpoint Inhibitor-Associated Colitis and a Short Review

Cited by 16 publications

References 31 publications

Immunological consequences of microbiome-based therapeutics

Immunological consequences of microbiome-based therapeutics

Immune-related adverse events in checkpoint blockade: Observations from human tissue and therapeutic considerations

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma

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