Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor

Abstract

IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

Immune‐related adverse events in non‐small cell lung cancer: Occurrence, mechanisms and therapeutic strategies

“…This observation was corroborated by another investigation involving 34 patients, indicating an inverse relationship between the prevalence of the Bacteroidetes phylum and the onset of CTLA4‐related colitis 139 . More recently, Hamada et al 149 . observed a higher abundance of Turicibacter and Acidaminococcus in the group of patients experiencing irAEs.…”

“…148 This observation was corroborated by another investigation involving 34 patients, indicating an inverse relationship between the prevalence of the Bacteroidetes phylum and the onset of CTLA4related colitis. 139 More recently, Hamada et al 149 observed a higher abundance of Turicibacter and Acidaminococcus in the group of patients experiencing irAEs. These findings collectively imply a potential mechanistic association between particular bacterial groups in the gut microbiota and irAEs, offering a promising target for novel anti-tumour immunotherapy.…”

“…As previously mentioned, the role of the gut microbiome is vital in maintaining homeostasis in the host's gut and other sites, significantly influencing the development of irAEs 145,154 . Consequently, the role of specific gut microbiomes is gaining increasing recognition 139,143,149 . Future research should focus on identifying specific microbiomes that can optimise the outcomes of cancer immunotherapy.…”

Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas

“… 24 These IDO inhibitor-treated animals, although they had a median survival slightly higher than the controls, their biota had significant levels of Turicibacter , which were not detected in the naive and PBS-treated animals but that certainly had to be present in the community to increase its abundance in this group. This taxon, often associated with a healthy host, including probiotic properties, has been found in association with ICI response 36 and anti-inflammatory effects. 37 …”

Anti-cancer management of head and neck cancers and oral microbiome—what can we clinically obtain?

“…Mann et al., in the in-cell line study, showed that microbiota via Toll-like receptor 2 may directly modulate the expression of PD-L1 in HNCs. In addition, the effect of the gut microbiome in response to ICIs was proven in many different types of epithelial tumors ( Routy et al., 2018 ; Zheng et al., 2019 ; Hamada et al., 2023 ). Currently, some studies registered in the Clinicaltrials.gov registry try to address directly or indirectly the issue of the link between microbiome in immunotherapy response (e.g., NCT05375266: recruiting, NCT05083416: active, not recruiting), which ought to be followed.…”