☆ 4.7 Review

The Role of the Innate Immune Response in Oral Mucositis Pathogenesis

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Baseline gut microbiota composition is associated with oral mucositis and tumour recurrence in patients with head and neck cancer: a pilot study

Ghanyah Al-Qadami et al.

Summary: This study aimed to uncover associations between an individual's pre-therapy gut microbiota and the severity of radiotherapy-induced oral mucositis (OM) as well as recurrence risk in patients with head and neck cancer (HNC). The results showed that the composition of the gut microbiota was associated with the severity of OM and the risk of HNC recurrence.

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Summary: Immune cells and commensal microbes in the human intestine communicate and react with each other to maintain healthy immune activities. Probiotic bacteria can stimulate immune cells and microflora to modulate immune functions and homeostasis. The use of probiotics has potential for improving immune system activities.

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Article Pharmacology & Pharmacy

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Summary: Chemotherapy-induced mucositis is a severe side effect in cancer patients, for which there is currently no effective supportive therapy. This study investigated the use of anakinra and dexamethasone as potential treatments for idarubicin-induced mucositis in rats. The results showed that anakinra alone can reverse the induced diarrhea and a combination of anakinra and dexamethasone can prevent the reduction of jejunal villus height. These findings suggest that anakinra and dexamethasone may serve as supportive therapies for chemotherapy-induced intestinal mucositis and diarrhea.

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY (2023)

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Review Immunology

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Hongzhi He et al.

Summary: The interaction between oral microbiota and innate immunity plays a vital role in the pathogenesis and development of oral diseases. Understanding the mechanisms of this interaction can lead to the development of novel therapies for preventing and treating oral diseases.

EXPERT REVIEW OF CLINICAL IMMUNOLOGY (2023)

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Review Biochemistry & Molecular Biology

From Pathogenesis to Intervention: The Importance of the Microbiome in Oral Mucositis

Julia S. Bruno et al.

Summary: Oral mucositis (OM) is a common and impactful toxicity of standard cancer therapy, largely caused by the destruction of epithelial cells and increased inflammation. Changes in the oral microbiome may contribute to the development and severity of OM, beyond opportunistic infections. This review analyzes the bacterial shift in cancer patients with OM through 16S rRNA gene sequencing, and explores the potential role of the patient's microbial fingerprint in OM development and prediction.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Biochemistry & Molecular Biology

Anti-Inflammatory Effects of β-Cryptoxanthin on 5-Fluorouracil-Induced Cytokine Expression in Human Oral Mucosal Keratinocytes

Hironaka Yamanobe et al.

Summary: Oral mucositis, a common side effect of chemotherapy, causes oral pain and affects patients' quality of life. The effects of beta-cryptoxanthin (beta-cry), a carotenoid found in citrus fruits with antioxidant and anti-inflammatory properties, on oral mucositis are unclear. In this study, we found that beta-cry can enhance cell proliferation and suppress the expression of inflammatory cytokines and matrix metalloproteinases induced by 5-fluorouracil (5-FU) in human normal oral mucosal keratinocytes (hOMK). These findings suggest that beta-cry can alleviate chemotherapy-induced oral mucositis when combined with oral care.

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Nurses' knowledge on assessment and management of cancer therapy-associated oral mucositis

Barnabas Manlokiya Raymond et al.

Summary: This study explored the baseline nursing knowledge on assessment and management of cancer therapy-associated oral mucositis (OM) in a tertiary hospital in Ghana. The findings revealed that nurses had insufficient knowledge on the standardized tool for OM assessment and lacked a definitive approach to prevent and treat OM. Insufficient knowledge on cancer treatment-associated mucositis, lack of structured protocol for OM, and unavailable tools for assessing the oral mucosa were identified as factors affecting the management of OM.

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H. R. Wardill et al.

Summary: High-dose chemotherapy can cause intestinal inflammation and breakdown of the mucosal barrier, leading to translocation of enteric pathogens. Antibiotics, the main treatment for these complications, have been found to have detrimental effects. This study shows that anakinra, an IL-1RA inhibitor, can minimize mucosal barrier injury and clinical symptoms in rats. The use of anakinra also leads to a more stable fecal microbiome composition. Additionally, anakinra has been proven safe in stem cell transplant patients. These results suggest that strengthening the mucosal barrier may be an effective strategy to mitigate the clinical consequences of high-dose chemotherapy.

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Review Immunology

Roles of Toll-Like Receptors in Radiotherapy- and Chemotherapy-Induced Oral Mucositis: A Concise Review

Ling Ji et al.

Summary: Radiotherapy and/or chemotherapy-induced oral mucositis (RIOM/CIOM) is a common complication in cancer patients. TLRs have a significant role in RIOM/CIOM and may serve as a novel mechanism for therapeutic interventions.

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Article Oncology

Association between Antibiotic Exposure and Systemic Immune Parameters in Cancer Patients Receiving Checkpoint Inhibitor Therapy

Mitchell S. von Itzstein et al.

Summary: Patients treated with antibiotics have worse outcomes from cancer immunotherapy, potentially due to the impact of antibiotics on the gut microbiome. This study found significant differences in immune parameters, including antibodies and cytokines, according to antibiotic exposure.

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Article Immunology

Distinctive microbiota of delayed healing of oral mucositis after radiotherapy of nasopharyngeal carcinoma

Rui Jiang et al.

Summary: This study suggests a potential association between oral microbiome and delayed healing of oral mucositis in patients with nasopharyngeal carcinoma (NPC). Actinobacteria and Veillonellaceae may serve as biomarkers to predict the risk of severe delayed healing of oral mucositis after radiotherapy.

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Clinical evaluation of toll-like receptor-5 agonist for radiation-induced oral mucositis in beagle dogs

Jaeeun Ko et al.

Summary: This study evaluated the clinical safety and radiomitigative effect of KMRC011 in beagle dogs with radiation-induced oral mucositis. The results suggest that KMRC011 may be used as an adjuvant for short-term radiotherapy without severe adverse effects.

FRONTIERS IN VETERINARY SCIENCE (2022)

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Article Biochemistry & Molecular Biology

The Effect of Intensity-Modulated Radiotherapy to the Head and Neck Region on the Oral Innate Immune Response and Oral Microbiome: A Prospective Cohort Study of Head and Neck Tumour Patients

Zahra Dorna Mojdami et al.

Summary: This study aimed to investigate the effects of radiation therapy (RT) on oral neutrophils (oPMNs) and the oral microbiome in patients undergoing head and neck tumor (HNT) treatment. The results showed that RT caused a significant decrease in oPMN counts and suppressed their activation state, while also altering the composition of the oral microbiome.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Precision medicine for risk prediction of oral complications of cancer therapy-The example of oral mucositis in patients receiving radiation therapy for cancers of the head and neck

Stephen T. Sonis

Summary: Oral complications of cancer therapy are common and affect patients' quality of life. Risk factors impact treatment outcomes and precision medicine can help optimize treatment plans by considering individualized response to specific treatments.

FRONTIERS IN ORAL HEALTH (2022)

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Oral-Gut Microbiome Axis in the Pathogenesis of Cancer Treatment-Induced Oral Mucositis

Ghanyah Al-Qadami et al.

Summary: Oral mucositis is a common and debilitating complication of cancer treatments, causing pain and impairing oral functions, which can lead to treatment interruption and negative impacts on quality of life and tumor prognosis. Understanding the pathogenesis of OM helps identify new targets for intervention or prevention, with the oral-gut microbiome axis playing an important role in the development of OM.

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Elise E. Bruning et al.

Summary: TLR4 is a highly conserved protein involved in innate immunity with distinct roles in epithelial and immune cells throughout the gastrointestinal tract. While epithelial cell expression of TLR4 contributes to maintaining homeostasis, promoting immunoglobulin A production, and regulating permeability, immune cell expression is centered on maturation of dendritic cells and priming the adaptive immune system. However, further research is needed to fully understand the impact of site-specific TLR4 expression on inflammation and disease progression.

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Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis

Kung-Ju Chen et al.

Summary: The study indicated that the overexpression of neutrophil elastase (NE) is a key feature in 5-FU-induced intestinal mucositis (FUIIM). Treatment with the specific NE inhibitor MPH-966 significantly reversed the adverse effects of 5-FU on body weight, food intake, and intestinal function. MPH-966 also restored the balance of gut microbiota, suggesting its potential as a treatment candidate for FUIIM.

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A hypothesis for the pathogenesis of radiation-induced oral mucositis: when biological challenges exceed physiologic protective mechanisms. Implications for pharmacological prevention and treatment

Stephen T. Sonis

Summary: Oral mucositis (OM) is a significant unmet need for patients receiving standard concomitant chemoradiation (CRT) regimens for head and neck cancers, with a complex pathogenesis involving oxidative stress. A hypothesis suggests that the mucosal damage in OM is mainly due to cumulative CRT-induced biological changes overwhelming physiological self-protective mechanisms, and an individual's ability to mount a protective response is determined by interactions between genomics, epigenomics, and microbiomics. Effective biologic or pharmacologic interventions for OM are likely to supplement or stimulate existing physiological damage-control mechanisms.

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Superoxide Dismutase as an Intervention for Radiation Therapy-Associated Toxicities: Review and Profile of Avasopasem Manganese as a Treatment Option for Radiation-Induced Mucositis

Stephen T. Sonis

Summary: Toxicities associated with radiation therapy can be effectively mitigated through interventions aimed at disrupting the biological cascade of toxicity development, with oxidative stress being a key initiator of normal tissue injury. Attempts to supplement endogenous superoxide dismutases or develop synthetic dismutase mimetics have shown some potential, with avasopasem manganese emerging as a promising dismutase mimetic in clinical trials for reducing severe oral mucositis in head and neck cancer patients undergoing chemoradiation.

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Article Medicine, General & Internal

Neutrophil-to-Lymphocyte Ratio as a Factor Predicting Radiotherapy Induced Oral Mucositis in Head Neck Cancer Patients Treated with Radiotherapy

Iwona Homa-Mlak et al.

Summary: The study revealed a positive correlation between NLR and the severity of OM, with higher NLR values associated with an increased risk of more severe OM. Additionally, higher TNM stage and NLR values were identified as independent prognostic factors for survival.

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Article Multidisciplinary Sciences

GM-1111 reduces radiation-induced oral mucositis in mice by targeting pattern recognition receptor-mediated inflammatory signaling

Abigail Pulsipher et al.

Summary: Radiation therapy causes tissue damages, leading to increased expression levels of PRRs and pro-inflammatory cytokine genes. GM-1111 significantly reduces the severity and incidence of OM by inhibiting downstream pro-inflammatory cytokine genes, without interfering with radiation therapy for HNC SCC-25 tumor regression.

PLOS ONE (2021)

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Sevda Senel

Summary: The oral mucosa, as the lining tissue of the oral cavity, serves as a critical barrier against pathogens and exogenous chemicals. The oral microbiota and immune system play vital roles in maintaining host health through interactions that affect homeostasis and disease.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Tissue Damage in Radiation-Induced Oral Mucositis Is Mitigated by IL-17 Receptor Signaling

Jessica Saul-McBeth et al.

Summary: Oral mucositis (OM) is a treatment-limiting adverse side effect of radiation and chemotherapy, with approximately 80% of patients undergoing radiotherapy for head and neck cancers developing OM. Studies suggest that IL-17 plays a protective role in OM through multiple mechanisms including restoration of damaged epithelia and control of neutrophil response.

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Oral microbiota transplantation fights against head and neck radiotherapy-induced oral mucositis in mice

Huiwen Xiao et al.

Summary: Oral mucositis is a common complication in NOALC patients undergoing radiotherapy, and oral microbiota transplantation can alleviate the symptoms. The gut microbiota also plays a role in oral mucositis progression. Additionally, specific oral microorganisms like Lactobacillaceae could potentially serve as biomarkers for predicting NOALC prognosis after radiotherapy.

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Anna Vesty et al.

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KMRC011, an agonist of toll-like receptor 5, mitigates irradiation-induced tissue damage and mortality in cynomolgus monkeys

Hong-Soo Lee et al.

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Vitaliana De Sanctis et al.

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Anura Ariyawardana et al.

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Elke Cario

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