Emile Voest

Immune checkpoint blockade (ICB) has shown promise in tumors with high tumor mutational burden (TMB), but the absence of formal EMA approval highlights a lack of strong supporting evidence.

Within the Drug Rediscovery Protocol, we tested the ICB combinations atezolizumab plus bevacizumab and nivolumab plus ipilimumab in patients with TMB-high tumors and found that durable benefit occurred mainly in those with TMB above 20 mutations per megabase.

Early treatment initiation further improved outcomes, while biomarker analysis linked adaptive immune infiltration to longer progression-free survival. These results point to refined TMB cut-offs and immune biomarkers as tools to better guide patient selection for ICB in clinical practice.

Not all cancer cells within a tumor are the same. They differ in their evolutionary history, and these differences can determine whether the immune system can recognize them. That is the key finding of our recently published study in Cancer Cell, made possible through the use of advanced organoid co-culture models that allowed functionally determining the extent of immune control at single subclone resolution. The results offer a possible explanation for why immunotherapy often fails to eliminate the whole tumor.

Our lab has recently published a number of papers, ranging from the relationship between the tumor microbiome and cancer metastasis, through the value of real-world data in oncology to the use of whole genome sequencing to discover biomarkers for immunotherapy. See some highlights of this exciting work below!