Super excited about our latest work on understanding how BMI impacts tumor outcomes and treatment response in #kidneycancer thelancet.com/journals/lanon….
This work was led by the awesome @ASanchez_UroOnc with generous grant support from @ConquerCancerFd and @sloan_kettering.
This work was led by the awesome @ASanchez_UroOnc with generous grant support from @ConquerCancerFd and @sloan_kettering.
A little background on our study. In 2013 in this study ncbi.nlm.nih.gov/pubmed/24285872 We initially found that higher BMI patients with localized ccRCC had better cancer specific outcomes. We linked this to unique transcriptomic profile of these tumors, including lower levels of FASN. 
Next, we collaborated with @DrChoueiri @DrDanielHeng and @AlbigesL where they showed that obese patient responded better to anti-VEGF therapy. ncbi.nlm.nih.gov/pubmed/27601543
We then read this excellent paper by @mcquadeMDLAc sciencedirect.com/science/articl…
Which showed that obese melanoma patient did better than non obese patients with both targeted therapies and immunotherapies.
Which showed that obese melanoma patient did better than non obese patients with both targeted therapies and immunotherapies.
To investigate this question in clear cell #kidneycancer, we worked with @motzermd and @GeneCollector amongst others to analyze both a large anti-VEGF and immunotherapy treated data set. The cool part is that we had both clinical, transcriptomic and IHC data for many tumors.
Beginning with the COMPARZ clinical trial (ncbi.nlm.nih.gov/pubmed/23964934) and the TCGA we found that higher BMI patients had better response to anti-VEGF therapy and this could be linked to higher angiogenesis gene signatures (Figure A and B).
Consistent higher angiogenic scores in both cohorts.
Intriguingly, these tumors had lower PDL1, and lower or non-different immune infiltration scores.
So, we were expecting to see these patients do worse with immunotherapy. But to our surprise, we found that the obese patients actually did much better (figure C) despite having immunologically "cold" RNA expression and lower PDL1.
To try to tease this apart, we looked at a really cool cohort of patients with both tumor and peritumoral fat, and compared the transcriptomes of both the obese and non obese patients.
Fascinatingly, the fat surrounding the obese tumors was much more immunologically "hot" perhaps explaining their sensitivity to immunotherapy!
Now, obviously this work is just beginning but we can confidently say that ccRCC tumors developing in obesogenic environments have high angiogenic signatures and are immunologically "cold" despite responding better to both anti-VEGF and immunotherapies. Stay tuned for more!
