Abstract 86P
Background
Obesity rivals smoking as a leading modifiable risk factor for cancer mortality, accounting for up to 20% of adult cancer-related deaths. Diet is a crucial factor in obesity development and significantly influences cancer growth. Paradoxically, high BMI has been linked to improved immune checkpoint inhibitor (ICI) efficacy in various cancers, challenging the notion that obesity is universally detrimental in cancer contexts. To address this paradox, we devised a panel of 12 diets that mimic human dietary patterns in mouse models, observing vastly different rates of cancer growth and ICI response. Surprisingly, not all obesity-inducing diets were beneficial for ICI, prompting an investigation into the cause of these disparities. The microbiome's pivotal role in regulating cancer and therapy through its profound influence on the immune system is well-supported, with gut dysbiosis and antibiotic use increasing cancer risk and blunting ICI response in patients and fecal microbial transplant from ICI-responsive patients shown to enhance ICI therapy. We propose that the interplay between diet and systemic inflammatory responses to gut microbiota contributes to the variations in ICI response across obesity-inducing diet models.
Methods
To track the gut microbial composition changes in mice during the development of our 12-diet model, we collected stool samples and performed 16s rRNA sequencing. The analyses focused on four obesity-inducing diets: American, High Fat, Ketogenic and Mediterranean.
Results
Analysis unveiled differences in gut bacterial composition at the phylum level across all four obesity inducing diets. However, family-level changes were associated with ICI response in a diet-specific manner. To delve deeper into these findings, we conducted metagenomic sequencing, revealing specific species associated with ICI response in preliminary analyses.
Conclusions
These findings suggest that diet-induced gut microbial modifications, in the context of obesity, may influence ICI efficacy, and offers promising avenues for the development of new therapeutic approaches that utilize the microbiome to enhance cancer treatment outcomes.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Canadian Cancer Society.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
94P - Harnessing circulating tumor DNA in bronchoalveolar lavage fluid for precise molecular diagnosis of NSCLC
Presenter: Frank Borm
Session: Cocktail & Poster Display session
Resources:
Abstract
95P - Automatic data processing to identify EGFR mutations in pathology reports of patients with non-small cell lung cancer (NSCLC)
Presenter: Betzabel Cajiao Garcia
Session: Cocktail & Poster Display session
Resources:
Abstract
96P - Analysis of concordance between microsatellite instability by next generation sequencing (NGS-MSI) and mismatch repair deficiency by immunohistochemistry (IHC-MMR) in endometrial cancer (EC) patients
Presenter: Simona Duranti
Session: Cocktail & Poster Display session
Resources:
Abstract
97P - Prospects of liquid biopsy in determining prognosis in children with HGG and DIPG
Presenter: Olga Regentova
Session: Cocktail & Poster Display session
Resources:
Abstract
98P - Liquid biopsy in NSCLC: A promising tool to predict immunotherapy response
Presenter: Ana Fernández
Session: Cocktail & Poster Display session
Resources:
Abstract
99P - Comprehensive genomic sequencing as an ancillary diagnostic tool for pathologists
Presenter: Dan Miller
Session: Cocktail & Poster Display session
Resources:
Abstract
100P - Standard serum biomarkers to help predict a cancer diagnosis in patients with non-specific symptoms: Data from Guy´s rapid diagnostic clinic
Presenter: Maria Monroy Iglesias
Session: Cocktail & Poster Display session
Resources:
Abstract
101P - Patient-derived organoids to optimize CDK4/6 inhibitor-based treatment selection in early breast cancer
Presenter: Carla Alves
Session: Cocktail & Poster Display session
Resources:
Abstract
102P - MicroRNAs in urine and saliva as non-invasive biomarkers of minimal residual disease in pediatric acute lymphoblastic leukemia
Presenter: Alejandra Pando-Caciano
Session: Cocktail & Poster Display session
Resources:
Abstract
103P - MSI detection by NGS using tumor samples and liquid biopsy for patients with solid tumors: A single institution experience
Presenter: Alexandra Lebedeva
Session: Cocktail & Poster Display session
Resources:
Abstract