Tumour assembloids recapitulate tumour-CAF-T cell crosstalk in renal cancer.

Tumour assembloids in humanized mouse models of renal cell carcinoma show CAF–CD8 T cell crosstalk is linked to anti-PD-1 responsiveness via a WNT→activin A axis.

• Why it matters: Current human models limit manipulation of multiple microenvironment components, leaving tumour–stroma–immune signalling and its impact on checkpoint inhibitor outcomes insufficiently understood.
• What they did: The study conditionally reconstituted cancer cells, CAFs, and tumour-infiltrating immune cells in combinatorial mix-and-match renal cancer assembloids, then used genetically engineered assembloids in humanized mouse models to probe mechanisms.
• The result: Tumour-derived WNT induces CAF activin A to maintain non-cell-autonomous CD8 T cell stemness and enhance sensitivity to PD-1 blockade, while WNT-unresponsive CAFs lacking activin A impair stemness and confer resistance.