Conclusions: We get a glimpse into the tumor black box. We see what an efficient anti-tumor immune response looks like. Which means we may: 1. Be able to tell if a treatment works or not, if we measure them. 2. Make treatments more efficient, if we find how to expand CRATERs.

Yes. Not only do they exist in great similarity to the zebrafish, CRATERs multiply during successful immunotherapy- when the patient presented clinical benefit post treatment. But there are extremely few CRATERs when treatment failed, even if the T cells entered the tumor.

It is in the CRATERs that we find multiple, lasting interactions of CD8+ T cells and melanoma, cell death, IFN-γ production. A battlefield. Indicating that the CRATERs are a major site for tumor killing following immunotherapy. Now the big question is- in human melanoma too?

Without treatment, CD8+ T cells don't harm tumors too much. But immunotherapy is aimed at activating CD8+ T cells against tumors. When we give immunotherapy these pockets–CRATERs; Cancer Regions of Antigen presentation and T cell engagement and Retention- come alive.

This behavior is characteristic of antigen recognition. Indeed, those pockets are rich with antigen presenting molecules, needed for the observed T cell retention. Simply put, the melanoma in those pockets shines bright to the T cells. And it has consequences during therapy.

And we found that infiltrating CD8+ T cells don’t just randomly distribute across the tumor. They go into pockets. But they are not stuck there (as we would have thought if it wasn’t a movie). They stay there for many hours interacting with melanoma cells and then move on. How come?

That’s a bit ambitious- how to see what is going on within the tumor? You could cut it and stain it, but even with the most sophisticated methods, you will lose a lot of information on tumor architecture and cellular dynamics.
Well, the zebrafish gave us a little advantage here.

🚨Publication alert: Where does immunotherapy happen? What can the fish teach us about human pathology? And a dendritic cell is having a friend for dinner. Cancer immunology goes live, now in @cp-cell.bsky.social.
Here is a concise summary of a pretty big study 🧵. Let’s go (appetizer👇)