Intestinal Microbiome Associated With Immune-Related Adverse Events for Patients Treated With Anti-PD-1 Inhibitors, a Real-World Study

Abstract

AimImmune checkpoint inhibitors (ICIs) have updated the treatment landscape for patients with advanced malignancies, while their clinical prospect was hindered by severe immune-related adverse events (irAEs). The aim of this study was to research the association between gut microbiome diversity and the occurrence of ICI-induced irAEs.Patients and MethodWe prospectively obtained the baseline fecal samples and clinical data from patients treated with anti-PD-1 inhibitors as monotherapy or in combination with chemotherapy or antiangiogenesis regardless of treatment lines. The 16S rRNA V3-V4 sequencing was used to test the gene amplicons of fecal samples. The development of irAEs was evaluated and monitored from the beginning of therapy based on CTCAE V5.01.ResultsA total of 150 patients were included in the study and followed up for at least 6 months. A total of 90 (60%) patients developed at least one type of adverse effect, among which mild irAEs (grades 1–2) occurred in 65 patients (72.22%) and severe irAEs (grades 3–5) in 25 patients (27.78%). Patients with severe irAEs showed a visible higher abundance of Streptococcus, Paecalibacterium, and Stenotrophomonas, and patients with mild irAEs had a higher abundance of Faecalibacterium and unidentified_Lachnospiraceae. With the aid of a classification model constructed with 5 microbial biomarkers, patients without irAEs were successfully distinguished from those with severe irAEs (AUC value was 0.66).ConclusionCertain intestinal bacteria can effectively distinguish patients without irAEs from patients with severe irAEs and provide evidence of gut microbiota as an informative source for developing predictive biomarkers to predict the occurrence of irAEs.

Neurological Manifestations Related to Immune Checkpoint Inhibitors: Reverse Translational Research by Using the European Real-World Safety Data

“…Actually, evidence concerning the pathogenesis of CNS toxicities following immune checkpoint blockade is growing but yet uncertain. It is well known how the gut microbiota can influence the immune system, influencing its possible response to ICI therapy ( 53 ). At same time, the mutual relationship between gut microbiota and neurologic disorders is widely recognized, since gut microbiota can interact with the CNS through the so-called microbiota–gut–brain axis ( 54 , 55 ).…”

“…In a recent real-world study, Wenhui Liu et al highlighted how the gut microbiome diversity influences the occurrence of ICI-induced irAEs, including peripheral neuritis associated with anti-PD-1 inhibitor use. According to their results, the gut microbiota can be considered as the source for developing predictive biomarkers useful to predict the occurrence of irAEs, especially in terms of event seriousness (53). Moreover, the presence of pre-existing subclinical autoimmunity phenomena might contribute to the occurrence of ICI-related immune complications, including nervous complications (58).…”

Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy

“…Other drugs, particularly broad-spectrum antibiotics, were also used. According to our previously published study ( 23 ), the follow-up lasted 6 months with regular clinic visits by an oncologist (Dr. Fang Ma) and two pharmacists (Pharm. Wenhui Liu and Pharm.…”

Interaction between gut microbiota and immune checkpoint inhibitor-related colitis

“…Mounting evidences illustrated that the bacteria exert direct effect via extracellular enzymes, lipopolysaccharide (LPS) and others in their interaction with IRC. Higher levels of Stenotrophomonas have been found in severe diarrhea patients receiving ICI treatment ( 21 ). Stenotrophomonas is considered an environmental bacterium commonly found in the respiratory or digestive tract.…”