Nice work!!

This dashboard is great. Could you pin it to the top of your feed, or add the link to your profile?

💔

Thanks Dagan!

This was a collaborative team effort! Thanks to Kavita Desai, Patricia Tiburcio, Austin Warne, and everyone else! Thanks also to funding from Pablove Foundation, Alex's Lemonade Stand, CPRIT, and NIH. And thanks to mentorship and support from @amatrudalab.bsky.social!

Or maybe we haven't been using the right therapy combinations. We've really only tried ICIs alone, but our data suggests that we should combine with conventional chemotherapy.

In fact, we've opened a clinical trial to test that exact question! www.utsouthwestern.edu/newsroom/art...

So: Why haven't childhood cancers responded to ICIs?

Maybe we haven't been treating the right patients. The single-agent trials in pediatrics tested these drugs against all types of solid tumors. But we show that certain tumors are more immune-enriched.

Lastly, using public data from adult cancers, we showed that microRNA pathway alterations were linked to immune gene expression signatures and better response to ICIs.

The immune subset was also enriched for beta-catenin and microRNA pathway mutations. We verified that Wnt signaling induced PD-L1 expression in Wilms tumor cells. We also showed that knocking down DROSHA or DICER1 in Wilms tumor cells caused a robust increase in PD-L1.

Chemotherapy-treated tumors were in this immune subset. In public RNA-seq from an independent group of tumors, chemo exposure was also associated with immune gene expression. In the lab, we found that some chemotherapies, like doxorubicin, were particularly effective at inducing PD-L1.

We studied Wilms tumor, the most common childhood kidney cancer, which has low mutational burden. Using protein arrays, we were surprised to find that about a subset show upregulation of immune markers.

Thanks for including me!