Esophageal squamous cell carcinoma (ESCC): could the gut mycobiota lend a hand?
Gut mycobiota profile could serve as a biomarker to predict responses to neoadjuvant immunochemotherapy in the treatment of esophageal squamous cell carcinoma. It could even inspire new therapeutic avenues.
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About this article
Neoadjuvant immunochemotherapy is seen as a major advance in the treatment of (sidenote: Esophageal Squamous Cell Carcinoma (ESCC) Type of esophageal carcinoma (EC) that can affect any part of the esophagus, but is usually located in the upper or middle third. The average age of onset of ESCC is between the ages of 60 to 70 years and it is more frequently seen in males. It is usually asymptomatic until an advanced disease stage with common presenting symptoms being dysphagia (at first with solids then progressing to fluids) and weight loss. Less commonly odynophagia, hoarseness of voice, coughing, or chest pain can be presenting features. Source : https://www.orpha.net/en/disease/detail/99977 ) . However, it remains difficult to predict which patients will respond favorably to it. Faced with this major challenge, the gut mycobiota appears to offer hope, a Chinese study having found that gut fungal signatures may serve as biomarkers.
Partially repaired dysbiosis
An analysis of fecal samples showed that 68 ESCC patients had a significant dysbiosis of the gut mycobiota prior to treatment compared to 19 healthy controls: reduced diversity, higher abundance of pathogenic fungi and lower presence of beneficial fungi, and less complex ecological networks, indicating fewer synergies. Treatment with neoadjuvant immunochemotherapy improves the diversity and richness of the fungal community and rebalances certain beneficial metabolic pathways, although without reaching the levels seen in healthy subjects.
1/29,400 Esophageal squamous cell carcinoma (ESCC) has an estimated annual incidence of 1/29,400 ¹.
0,1% Although fungi make up less than 0.1% of the microbiome, they possess unique metabolic features that contribute to host functions ².
A mycobiota that predicts success
Most importantly, the profiles of the mycobiota sampled prior to treatment make it possible to distinguish future responders from non-responders. Responders have higher fungal diversity before treatment, more stable networks, suggesting greater resilience, and higher abundance of beneficial fungi (including Candida boidinii) correlated with “hot” tumor signatures (stimulation of T-helper 1 cells, pro-inflammatory cytokines, elevated cytotoxic markers).
What about non-responders? Their mycobiota was enriched in immunosuppressive species associated with characteristics of “cold” tumors (Th-2 cells, immunosuppressive cytokines).
Thus, the mycobiota of responders appears to promote immunity that contributes to tumor phenotypes favorable to the success of immunotherapy, while that of non-responders may contribute to tumor microenvironments that are resistant to immunotherapy.
What is the survival rate for patients with ESCC?
As ESCC is usually diagnosed at an advanced disease stage, the overall prognosis is poor, with an overall 5-year survival of between 10-20%. In patients treated with curative intent the cure rate currently approaches 40% 1.
Predict... and modulate response to treatment
Lastly, the mycobiota appears to be able to accurately and robustly predict future treatment efficacy, with the (sidenote: Area under the curve (AUC) Indication of the discriminatory power of a classification model, for example, an AUC of 1.0 indicates a perfect classifier. It is the probability that the classification model will correctly classify a positive sample. ) reaching 82.9% (genus-level) and even 87.4% (species-level). The Saccharomyces genus appears to be the most robust predictor of non-response. These results suggest that the gut mycobiota may ultimately serve as a biomarker for stratifying patients in ESCC treatment.
Another potential application? Optimizing the results of immunotherapy, with the fungi identified, whether beneficial or harmful, representing targets for modulating the microbiota. The researchers’ initial findings show that administration of Candida boidinii enhanced the efficacy of anti-PD-1 therapy in mice. Could beneficial fungi one day improve treatment responses in patients with ESCC?
