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

Bouferraa, Youssef; Chedid, Andrea; Amhaz, Ghid; Lakkiss, Ahmed El; Mukherji, Deborah; Temraz, Sally; Shamseddine, Ali

doi:10.3390/ijms22158036

Cited by 12 publications

(21 citation statements)

References 147 publications

(281 reference statements)

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“…Microbial metabolites are also known to regulate the immune response to cancer. Butyrate was one of the first bacterial products implicated in cancer progression and response to immune therapy ( 66 ). Novel metabolites and mechanisms of action have been recently described.…”

Section: Discussionmentioning

confidence: 99%

The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone

Pal¹,

Perrien²,

Yumoto³

et al. 2022

Journal of Clinical Investigation

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Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to the bone marrow (BM) in bone metastasis, blockade of S1P-mediated intestinal egress of NK and Th1 cells, or inhibition of their CXCR3/CXCL9-mediated influx into the BM, prevented the expansion of BM NK and Th1 cells and accelerated tumor growth and osteolysis. Using a mouse model, this study revealed mechanisms of microbiota-mediated gut-bone crosstalk that are relevant to the immunological restraint of melanoma metastasis and tumor growth in bone. Microbiome modifications induced by antibiotics might have negative clinical consequences in patients with melanoma.

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Section: Discussionmentioning

confidence: 99%

The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone

Pal¹,

Perrien²,

Yumoto³

et al. 2022

Journal of Clinical Investigation

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“…This result has distinct proteomic and metabolomic signatures and confirmed that the gut microbiome regulates these changes. [11] The restoration of the microbiome ecosystem might improve the symptoms of steroid-refractory patients. Therefore, to improve the steroid-refractory state, stool from a healthy male was transplanted.…”

Section: Discussionmentioning

confidence: 99%

The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome

et al. 2022

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Rationale: Cronkhite-Canada syndrome (CCS) is a rare non-hereditary disease of unknown etiology that is characterized by the appearance of multiple polyps in the entire gastrointestinal (GI) tract, except in the esophagus, with GI and non-GI symptoms. Various factors are associated with the pathogenesis of CCS. Immune dysregulation has been discussed as one of the pathogeneses of CCS, and dysbiosis of the gut microbiota can affect the immune system. Currently, standard treatment has not been established. Patient concerns and diagnosis:We present the treatment with fecal microbiota transplantation (FMT) in a 67-year-old male patient with steroid-refractory CCS who could not undergo anti-tumor necrosis factor-a treatment due to suspected tuberculosis infection.Interventions: FMT has recently attracted attention as a method of overcoming drug resistance through immunomodulatory effects through microbiome regulation. We collected the patient's stool samples before FMT and 8 weeks after FMT.Outcomes: We analyzed the microbiome composition of patients by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). After FMT, the number of episodes of diarrhea and hypoalbuminemia were also corrected. The Chao 1 index after FMT, which was significantly higher than that of donors before FMT, changed to a similar level for donors after FMT. Fusobacterium nucleatum, Pyramidobacter piscolens, and Campylobacter concisus disappeared after FMT, suggesting the presence of an association between gut microbiota and CCS.Lessons: Furthermore, we provide the possibility that microbiome modulation by FMT could serve as a complementary treatment in patients with steroid-refractory CCS.

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“…This became relevant when some favorable bacteria were found to be associated with decreased peripheral Treg levels, thereby halting the suppression of the lymphocyte. These low levels of Treg seemed to correlate with good response to immunotherapy, further drawing an association between bacteria and response to treatment [ 85 ]. The communication between gut microbiota and immunological response could possibly be mediated by products of bacteria metabolism [ 85 ].…”

Section: Novel Therapeutic Approaches In Management Of Urological Dis...mentioning

confidence: 99%

The Urogenital System’s Role in Diseases: A Synopsis

Zerdan

Moukarzel

Naji

et al. 2022

Cancers

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The human microbiota contains ten times more microbial cells than human cells contained by the human body, constituting a larger genetic material than the human genome itself. Emerging studies have shown that these microorganisms represent a critical determinant in human health and disease, and the use of probiotic products as potential therapeutic interventions to modulate homeostasis and treat disease is being explored. The gut is a niche for the largest proportion of the human microbiota with myriad studies suggesting a strong link between the gut microbiota composition and disease development throughout the body. More specifically, there is mounting evidence on the relevance of gut microbiota dysbiosis in the development of urinary tract disease including urinary tract infections (UTIs), chronic kidney disease, and kidney stones. Fewer emerging reports, however, are suggesting that the urinary tract, which has long been considered ‘sterile’, also houses its unique microbiota that might have an important role in urologic health and disease. The implications of this new paradigm could potentially change the therapeutic perspective in urological disease.

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

Cited by 12 publications

References 147 publications

The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone

The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone

The first report on effect of fecal microbiota transplantation as a complementary treatment in a patient with steroid-refractory Cronkhite-Canada syndrome

The Urogenital System’s Role in Diseases: A Synopsis

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