Abstract 74P
Background
Globally, more people are overweight/obese than underweight, and obesity is associated with increased risk and mortality of at least 13 types of cancer. Paradoxically, obesity is not detrimental in all cancer contexts. For example, obesity is associated with improved immune checkpoint inhibitor (ICI) efficacy in a variety of cancer types. While there is a body of literature demonstrating that the gut microbiome impacts ICI efficacy in preclinical models and human clinical trials, it is unknown how these observations relate to dietary habits and/or body weight.
Methods
To investigate how diet influences cancer progression, we exposed our preclinical mouse model of lung cancer to 12 unique diets that lead to varying amounts of weight gain and metabolic dysfunction over 15 weeks. To identify biological mechanisms driving ICI sensitivity, we characterized peripheral blood and tumor-infiltrating immune cells by spectral flow cytometry. To identify diet-induced intestinal bacteria signatures, we performed 16s rRNA sequencing to profile the gut microbiota.
Results
We found that tumor growth and anti-PD-1 sensitivity are diet-dependent and vary significantly between obesity-promoting diets. Flow cytometric analysis of the peripheral blood revealed an inverse correlation between T cells and weight gain, and positive correlation with monocyte populations. However, these immune changes at-steady state were not associated with tumor growth or ICI sensitivity. Interestingly, the gut microbiome stabilized after only 3 weeks following diet enrollment, independent of significant weight gain over the diet enrollment period. Further, 3 weeks on diet was sufficient to phenocopy tumor growth kinetics observed after 15 weeks of diet, independent of any major bodyweight changes.
Conclusions
These findings suggest that diet-induced changes to the gut microbiome may be driving differences in tumor growth and ICI sensitivity, and that diet and nutrition can be optimized to maximize the patient population that can benefit from ICI therapy.
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
10P - An adapted CGP-based model to interpret POLE mutations in endometrial cancer
Presenter: Rita Trozzi
Session: Cocktail & Poster Display session
Resources:
Abstract
11P - Reconstructing tumour evolution of single cells using both somatic mutations and copy-number alterations
Presenter: Rija Zaidi
Session: Cocktail & Poster Display session
Resources:
Abstract
12P - Swiss-PO: Molecular modelling for precision oncology
Presenter: Fanny Krebs
Session: Cocktail & Poster Display session
Resources:
Abstract
13P - A novel algorithm for predicting variant detectability in oncogenomic analysis
Presenter: Alper Akkuş
Session: Cocktail & Poster Display session
Resources:
Abstract
14P - expHRD: An algorithm for the transcriptome-based estimation of homologous recombination deficiency score
Presenter: Jin-Ku Lee
Session: Cocktail & Poster Display session
Resources:
Abstract
15P - ClinBioNGS: An integrated clinical bioinformatics pipeline for the analysis of somatic NGS cancer panels
Presenter: Xavier Sole
Session: Cocktail & Poster Display session
Resources:
Abstract
16P - Investigation of c-MYC role in DNA-PK-mediated activation of STING pathway in SCLC
Presenter: Caterina de Rosa
Session: Cocktail & Poster Display session
Resources:
Abstract
17P - NRF2 activation promotes HER2-targeted tolerance and resistance in oesophageal adenocarcinoma through metabolic reprogramming to glutathione
Presenter: Wei Zhang
Session: Cocktail & Poster Display session
Resources:
Abstract
18P - AURKB inhibition radiosensitises NSCLC by altering mitotic fate
Presenter: Kathryn Egerton
Session: Cocktail & Poster Display session
Resources:
Abstract
19P - Stratified control study on neuroendocrine differentiation and potential clinical markers in patients with limited-stage small-cell lung cancer
Presenter: Li Liu
Session: Cocktail & Poster Display session
Resources:
Abstract